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27 results on '"MESH: Trophoblasts"'

1. Pan-Genomic Regulation of Gene Expression in Normal and Pathological Human Placentas

Author

Clara Apicella, Camino S. M. Ruano, Basky Thilaganathan, Asma Khalil, Veronica Giorgione, Géraldine Gascoin, Louis Marcellin, Cassandra Gaspar, Sébastien Jacques, Colin E. Murdoch, Francisco Miralles, Céline Méhats, Daniel Vaiman, Des gamètes à la naissance : génomique, épigénétique et physiopathologie de la reproduction | From Gametes To Birth (FGTB), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and European Project: 765274,H2020-MSCA-ITN-2017,iPLACENTA(2018)

Subjects
preeclampsia, MESH: Humans, MESH: Pregnancy, placenta, expression Quantitative Trait Loci, MESH: Trophoblasts, MESH: Transcriptome, MESH: Genomics, [SDV]Life Sciences [q-bio], General Medicine, MESH: Placenta, MESH: Female, MESH: Gene Expression Regulation
Abstract

International audience; In this study, we attempted to find genetic variants affecting gene expression (eQTL = expression Quantitative Trait Loci) in the human placenta in normal and pathological situations. The analysis of gene expression in placental diseases (Pre-eclampsia and Intra-Uterine Growth Restriction) is hindered by the fact that diseased placental tissue samples are generally taken at earlier gestations compared to control samples. The difference in gestational age is considered a major confounding factor in the transcriptome regulation of the placenta. To alleviate this significant problem, we propose here a novel approach to pinpoint disease-specific cis-eQTLs. By statistical correction for gestational age at sampling as well as other confounding/surrogate variables systematically searched and identified, we found 43 e-genes for which proximal SNPs influence expression level. Then, we performed the analysis again, removing the disease status from the covariates, and we identified 54 e-genes, 16 of which are identified de novo and, thus, possibly related to placental disease. We found a highly significant overlap with previous studies for the list of 43 e-genes, validating our methodology and findings. Among the 16 disease-specific e-genes, several are intrinsic to trophoblast biology and, therefore, constitute novel targets of interest to better characterize placental pathology and its varied clinical consequences. The approach that we used may also be applied to the study of other human diseases where confounding factors have hampered a better understanding of the pathology.

Published
2023

2. Soluble CD146 is increased in preeclampsia and interacts with galectin-1 to regulate trophoblast migration through VEGFR2 receptor

Author

Ahmad Joshkon, Alexandrine Foucault-Bertaud, Wael Traboulsi, Christophe Demattei, Françoise Dignat-George, Nadia Alfaidy, Richard Bachelier, Odile Paulmyer-Lacroix, Jean-Christophe Gris, Aurélie S. Leroyer, Marcel Blot-Chabaud, Sylvie Bouvier Pharm, V. Letouzey, Nathalie Bardin, Mathieu Fortier, Sandra M. Blois, Marie Nollet, Eve Mousty, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Mécanisme de l’Angiogenèseet des BarrièresBiologiques (MAB2), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Sechenov First Moscow State Medical University, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Institut de Recherches en Technologies et Sciences pour le Vivant (IRTSV), and GRIS, Jean-Christophe

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Galectin 1, MESH: Pre-Eclampsia, MESH: Trophoblasts, CD146 Antigen, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Preeclampsia, Andrology, MESH: Pregnancy, Pre-Eclampsia, Trophoblast migration, Pregnancy, Galectin-1, Blocking antibody, Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target, medicine, Humans, Prospective Studies, Receptor, reproductive and urinary physiology, MESH: Galectin 1, MESH: Humans, Eclampsia, business.industry, Trophoblast, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, Trophoblasts, MESH: Prospective Stufies, carbohydrates (lipids), [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.anatomical_structure, CD146/sCD146, Female, Signal transduction, MESH: CD146 Antigen, business, MESH: Female
Abstract

International audience; Objective: To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1 (Gal1) in placenta-mediated complications of pregnancy.Design: Prospective pilot and experimental studies.Setting: University-affiliated hospital and academic research laboratory.Patient(s): One hundred fifteen women divided into three groups: 30 healthy, nonpregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications.Intervention(s): Wound-healing experiments were conducted to study trophoblast migration.Main outcome measure(s): Quantification of sCD146 and Gal1 by enzyme-linked immunosorbent assay. Analysis of trophoblast migration by wound closure.Result(s): Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies compared with nonpregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. In contrast, in women with preeclampsia, we found significantly higher sCD146 concentrations compared with women with normal pregnancies and no modification of Gal1. We emphasize the opposing effects of sCD146 and Gal, since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated with the use of an anti-CD146 blocking antibody or the use of small interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146, further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and inhibited its secretion, suggesting that sCD146 acts as a ligand trap.Conclusion(s): Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target. Clinical trial registration number: NCT 01736826.Trial registration: ClinicalTrials.gov NCT01736826.

Published
2022

3. PD-1 is expressed by and regulates human group 3 innate lymphoid cells in human decidua

Author

Emanuela Marcenaro, Marco Greppi, Enrico Munari, Paola Vacca, Maria Cristina Mingari, Alessandro Moretta, Silvia Pesce, Lorenzo Moretta, Ezio Fulcheri, Daniel Olive, Department of Experimental Medicine - DIMES [Genoa, Italy] (DIMES), University of Genoa (UNIGE), Department of Experimental Medicine, University of Genoa, D.I.C.M.I., Universita degli studi di Genova, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale per la Ricerca sul Cancro, Genova, Immunologia, Università di Genova, Dipartimento di Medicina Sperimentale, IRCCS Istituto Giannina Gaslini, Genova, and Università degli studi di Genova = University of Genoa (UniGe)

Subjects
MESH: Signal Transduction, 0301 basic medicine, MESH: Trophoblasts, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, B7-H1 Antigen, MESH: Decidua, Immune tolerance, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, MESH: B7-H1 Antigen, Homeostasis, Innate, Immunology and Allergy, Lymphocytes, Receptor, Hepatitis A Virus Cellular Receptor 2, MESH: Cytokines, Innate lymphoid cell, Decidua, MESH: Programmed Cell Death 1 Receptor, Trophoblasts, MESH: Placental Circulation, 3. Good health, Cell biology, medicine.anatomical_structure, MESH: Homeostasis, Cytokines, Female, MESH: Immunity, Innate, Signal transduction, Signal Transduction, Programmed cell death, MESH: Immune Tolerance, T cell, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Immune system, Immune Tolerance, medicine, Humans, Placental Circulation, MESH: Humans, Immunity, Immunity, Innate, MESH: Hepatitis A Virus Cellular Receptor 2, 030104 developmental biology, MESH: Lymphocytes, MESH: Female, 030215 immunology
Abstract

International audience; Group 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-α, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.

Published
2019

4. Peroxisome proliferator‐activated receptor gamma‐ligand‐binding domain mutations associated with familial partial lipodystrophy type 3 disrupt human trophoblast fusion and fibroblast migration

Author

Shoaito, Hussein, Chauveau, Sabine, Gosseaume, Camille, Bourguet, William, Vigouroux, Corinne, Vatier, Camille, Pienkowski, Catherine, Fournier, Thierry, Degrelle, Séverine, Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], PremUp Foundation, Institut de Recherche pour le Développement (IRD)-CHI Créteil-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris Cité (UPCité), Inovarion, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Institut de Recherche pour le Développement (IRD)-CHI Créteil-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), and Gestionnaire, Hal Sorbonne Université

Subjects
Models, Molecular, trophoblast differentiation, MESH: Mutation, endocrine system diseases, cell migration, MESH: Trophoblasts, Placenta, [SDV]Life Sciences [q-bio], Ligands, Mice, Protein Domains, Cell Movement, MESH: Ligands, Animals, Humans, MESH: Animals, MESH: Cell Movement, MESH: Mice, cell fusion, MESH: Humans, nutritional and metabolic diseases, Original Articles, Fibroblasts, Lipodystrophy, Familial Partial, Trophoblasts, PPAR gamma, [SDV] Life Sciences [q-bio], MESH: PPAR gamma, MESH: Fibroblasts, MESH: Cell Fusion, Mutation, embryonic structures, NIH 3T3 Cells, PPARG, MESH: Lipodystrophy, Familial Partial, MESH: Protein Domains, Original Article, MESH: Models, Molecular, familial partial lipodystrophy type 3 (FPLD3), MESH: NIH 3T3 Cells
Abstract

International audience; The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is essential for placental development, and alterations in its expression and/or activity are associated with human placental pathologies such as pre-eclampsia or IUGR. However, the molecular regulation of PPARG in cytotrophoblast differentiation and in the underlying mesenchyme remains poorly understood. Our main goal was to study the impact of mutations in the ligand-binding domain (LBD) of the PPARG gene on cytotrophoblast fusion (PPARGE352Q ) and on fibroblast cell migration (PPARGR262G /PPARGL319X ). Our results showed that, compared to cells with reconstituted PPARGWT , transfection with PPARGE352Q led to significantly lower PPARG activity and lower restoration of trophoblast fusion. Likewise, compared to PPARGWT fibroblasts, PPARGR262G /PPARGL319X fibroblasts demonstrated significantly inhibited cell migration. In conclusion, we report that single missense or nonsense mutations in the LBD of PPARG significantly inhibit cell fusion and migration processes.

Published
2020

5. Single Circulating Fetal Trophoblastic Cells Eligible for Non Invasive Prenatal Diagnosis: the Exception Rather than the Rule

Author

Cyril Goizet, Patrick Calvas, Marie-Claire Vincent, Claire Guissart, Virginie Dorian, Nicolas Molinari, Caroline Rooryck-Thambo, Cathy Liautard-Haag, Annabelle Chaussenot, Romain Favre, Catherine Alix-Panabières, Sandra Pierredon, Laetitia Monteil, Philippe Khau Van Kien, Mélanie Fradin, Amandine Boureau-Wirth, Marion Imbert-Bouteille, Emmanuelle Haquet, Elsa Le Boette, Yuliya Petrov, Jacques Puechberty, Cécile Zordan, Céline Moutou, Laure Cayrefourcq, Cécile Rouzier, Marjolaine Willems, Claire Miry, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Strasbourg, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Colombière, CHU de Bordeaux Pellegrin [Bordeaux], Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôptaux universitaires de Strasbourg (HUS), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre hospitalier Saint-Brieuc, and Salvy-Córdoba, Nathalie

Subjects
0301 basic medicine, MESH: Trophoblasts, Molecular biology, lcsh:Medicine, Diseases, Disease, Cell Separation, 0302 clinical medicine, Trinucleotide Repeats, Prenatal Diagnosis, lcsh:Science, MESH: High-Throughput Nucleotide Sequencing, Genetics, Whole Genome Amplification, 030219 obstetrics & reproductive medicine, Multidisciplinary, Molecular medicine, High-Throughput Nucleotide Sequencing, Trophoblasts, Huntington Disease, Microsatellite, Single-Cell Analysis, Biotechnology, MESH: Trinucleotide Repeats, Cell biology, Prenatal diagnosis, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Cell Separation, Article, 03 medical and health sciences, Medical research, Fetus, Multiplex polymerase chain reaction, Humans, Allele, MESH: Prenatal Diagnosis, Genotyping, MESH: Humans, Point mutation, lcsh:R, Health care, MESH: Fetus, MESH: Huntington Disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Feasibility Studies, lcsh:Q, MESH: Feasibility Studies, MESH: Single-Cell Analysis
Abstract

Non-Invasive Prenatal Diagnosis (NIPD), based on the analysis of circulating cell-free fetal DNA (cff-DNA), is successfully implemented for an increasing number of monogenic diseases. However, technical issues related to cff-DNA characteristics remain, and not all mutations can be screened with this method, particularly triplet expansion mutations that frequently concern prenatal diagnosis requests. The objective of this study was to develop an approach to isolate and analyze Circulating Trophoblastic Fetal Cells (CFTCs) for NIPD of monogenic diseases caused by triplet repeat expansion or point mutations. We developed a method for CFTC isolation based on DEPArray sorting and used Huntington’s disease as the clinical model for CFTC-based NIPD. Then, we investigated whether CFTC isolation and Whole Genome Amplification (WGA) could be used for NIPD in couples at risk of transmitting different monogenic diseases. Our data show that the allele drop-out rate was 3-fold higher in CFTCs than in maternal cells processed in the same way. Moreover, we give new insights into CFTCs by compiling data obtained by extensive molecular testing by microsatellite multiplex PCR genotyping and by WGA followed by mini-exome sequencing. CFTCs appear to be often characterized by a random state of genomic degradation.

Published
2020

6. Tissue-specific and SRSF1-dependent splicing of fibronectin, a matrix protein that controls host cell invasion

Author

Isabel C. Lopez-Mejia, Jamal Tazi, Jean Marie Blanchard, Virginie Deleuze, Marie-Luce Vignais, Flavio Della Seta, Marion de Toledo, Christian Jorgensen, Cosette Rebouissou, Patrick Fafet, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Lausanne (UNIL), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1), Hôpital Lapeyronie [Montpellier] (CHU), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vignais, Marie-Luce, and Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Trophoblasts, [SDV]Life Sciences [q-bio], Placenta, Endometrium, MESH: Serine-Arginine Splicing Factors, Exon, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, MESH: Fibronectins, MESH: Gene Expression Regulation, Developmental, MESH: Placentation, Nuclear protein, MESH: Organ Specificity, reproductive and urinary physiology, 0303 health sciences, biology, Serine-Arginine Splicing Factors, MESH: Alternative Splicing, Gene Expression Regulation, Developmental, Nuclear Proteins, RNA-Binding Proteins, Articles, MESH: Placenta, female genital diseases and pregnancy complications, Cell biology, Trophoblasts, [SDV] Life Sciences [q-bio], MESH: Endometrium, medicine.anatomical_structure, Cell Biology of Disease, Organ Specificity, 030220 oncology & carcinogenesis, RNA splicing, embryonic structures, MESH: Abortion, Induced, Female, medicine.medical_specialty, Primary Cell Culture, MESH: Primary Cell Culture, 03 medical and health sciences, Splicing factor, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Molecular Biology, 030304 developmental biology, MESH: Humans, Alternative splicing, Trophoblast, Abortion, Induced, MESH: Neoplasm Invasiveness, Cell Biology, Placentation, Fibronectins, Fibronectin, Alternative Splicing, MESH: RNA-Binding Proteins, Endocrinology, biology.protein, MESH: Female, MESH: Nuclear Proteins
Abstract

Matching sets of human primary fibroblasts cocultured with placenta explants are used to compare tissue capacities to support trophoblast invasion. Substituting endometrium with dermis dramatically reduces EVCT interstitial invasion, a phenomenon related to the ECM fibronectin content, FN alternative splicing, and expression of the SR protein SRSF1., Cell invasion targets specific tissues in physiological placental implantation and pathological metastasis, which raises questions about how this process is controlled. We compare dermis and endometrium capacities to support trophoblast invasion, using matching sets of human primary fibroblasts in a coculture assay with human placental explants. Substituting endometrium, the natural trophoblast target, with dermis dramatically reduces trophoblast interstitial invasion. Our data reveal that endometrium expresses a higher rate of the fibronectin (FN) extra type III domain A+ (EDA+) splicing isoform, which displays stronger matrix incorporation capacity. We demonstrate that the high FN content of the endometrium matrix, and not specifically the EDA domain, supports trophoblast invasion by showing that forced incorporation of plasma FN (EDA–) promotes efficient trophoblast invasion. We further show that the serine/arginine-rich protein serine/arginine-rich splicing factor 1 (SRSF1) is more highly expressed in endometrium and, using RNA interference, that it is involved in the higher EDA exon inclusion rate in endometrium. Our data therefore show a mechanism by which tissues can be distinguished, for their capacity to support invasion, by their different rates of EDA inclusion, linked to their SRSF1 protein levels. In the broader context of cancer pathology, the results suggest that SRSF1 might play a central role not only in the tumor cells, but also in the surrounding stroma.

Published
2013

7. The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF-trophoblast-IL-10 axis via Stat1 inhibition and Stat3 activation

Author

Jovane Hamelin-Morrissette, Julie Girouard, Christian Carrier, Julie Lafond, Angham Dallagi, Rachel Dadzie, Cathy Vaillancourt, Laetitia Laurent, Carlos Reyes-Moreno, Université du Québec à Trois-Rivières (UQTR), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), BioMed Research Centre [Montréal], Institut National de la Recherche Scientifique [Québec] (INRS)-Université du Québec à Trois-Rivières (UQTR)-Université du Québec à Montréal = University of Québec in Montréal (UQAM), Centre Hospitalier Régional de Trois-Rivières, and This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT) and the Réseau Québécois en Reproduction (RQR) to CR-M AD, RD and JH-M were supported by the RQR-CREATE scholarships program. JG holds a postdoctoral fellowship from the Fonds de la Recherche en Santé du Québec (FRSQ).

Subjects
MESH: Interleukin-10, MESH: Trophoblasts, [SDV]Life Sciences [q-bio], gestational fac, MESH: Monocytes, Leukemia Inhibitory Factor, Monocytes, MESH: Pregnancy, Pregnancy, Immunology and Allergy, Cytotoxic T cell, Macrophage, MESH: Chorionic Villi, reproductive and urinary physiology, biology, MESH: STAT3 Transcription Factor, MESH: Macrophage Activation, macrophage deac, MESH: Gene Expression Regulation, Cell biology, Interleukin-10, Trophoblasts, Interleukin 10, Infectious Diseases, medicine.anatomical_structure, STAT1 Transcription Factor, embryonic structures, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, embryonic cell, Chorionic Villi, Research Article, STAT3 Transcription Factor, medicine.medical_specialty, inflammatory ce, MESH: Cell Line, Tumor, MESH: Interferon-gamma, CD14, Immunology, Interferon-gamma, Internal medicine, Cell Line, Tumor, medicine, Humans, CD40, MESH: Humans, Monocyte, Macrophages, Trophoblast, MESH: Macrophages, Macrophage Activation, MESH: Leukemia Inhibitory Factor, Endocrinology, Gene Expression Regulation, biology.protein, cell migration, MESH: STAT1 Transcription Factor, Leukemia inhibitory factor, MESH: Female
Abstract

International audience; Interferon gamma (IFN-γ) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-γ induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-γ on macrophage activation. IFN-γ reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT+LIF cells) and BeWo cells (BW/ST+LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-γ. vCT+LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST+LIF cells reduce cell proliferation but enhance the migratory responses of monocytes. In addition, these factors reverse the inhibitory effect of IFN-γ on monocyte/macrophage motility. BW/ST+LIF cells also generate IFN-γ-activated macrophages with enhanced IL-10 expression, but reduced tumor-necrosis factor alpha (TNF-α), CD14 and CD40 expression as well as impaired cytotoxic function. Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-γ-induced Stat1 activation. These in vitro studies are the first to describe the regulatory role of the LIF-trophoblast-IL-10 axis in the process of macrophage activation in response to pro-inflammatory cytokines.

Published
2015

8. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake

Author

Drucilla J. Roberts, Nafisa K. Dajani, Coedy Hadden, Curtis L. Lowery, Preeti Singh, Yicong Li, Charles P. Mercado, Pamela Murphy, Fusun Kilic, Luc Maroteaux, Departments of Biochemistry and Molecular Biology, and Pharmacology and Toxicology, University of Arkansas for Medical Sciences (UAMS), Dept Pathology, Massachusetts General Hospital, Boston, MA 02114, Massachusetts General Hospital [Boston], Institut du Fer à Moulin, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Signal Transduction, Glycosylation, MESH: Trophoblasts, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Down-Regulation, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Insulin, MESH: Serotonin Plasma Membrane Transport Proteins, Serotonin transporter, MESH: Diabetes, Gestational, Serotonin Plasma Membrane Transport Proteins, 0303 health sciences, Multidisciplinary, biology, MESH: Glycosylation, Trophoblasts, medicine.anatomical_structure, PNAS Plus, embryonic structures, Female, MESH: Membrane Proteins, MESH: Molecular Chaperones, Signal Transduction, Adult, medicine.medical_specialty, Serotonin, Adolescent, Down-Regulation, MESH: Insulin, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Placenta, medicine, Humans, 030304 developmental biology, MESH: Adolescent, MESH: Humans, Endoplasmic reticulum, Trophoblast, Membrane Proteins, Transporter, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Insulin receptor, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Diabetes, Gestational, Endocrinology, chemistry, MESH: Protein Processing, Post-Translational, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Serotonin, MESH: Female, Protein Processing, Post-Translational, 030217 neurology & neurosurgery, Molecular Chaperones
Abstract

International audience; Serotonin (5-HT) transporter (SERT) regulates the level of 5-HT in placenta. Initially, we found that in gestational diabetes mellitus (GDM), whereas free plasma 5-HT levels were elevated, the 5-HT uptake rates of trophoblast were significantly down-regulated, due to impairment in the translocation of SERT molecules to the cell surface. We sought to determine the factors mediating the down-regulation of SERT in GDM trophoblast. We previously reported that an endoplasmic reticulum chaperone, ERp44, binds to Cys200 and Cys209 residues of SERT to build a disulfide bond. Following this posttranslational modification, before trafficking to the plasma membrane, SERT must be dissociated from ERp44; and this process is facilitated by insulin signaling and reversed by the insulin receptor blocker AGL2263. However, the GDM-associated defect in insulin signaling hampers the dissociation of ERp44 from SERT. Furthermore, whereas ERp44 constitutively occupies Cys200/Cys209 residues, one of the SERT glycosylation sites, Asp208 located between the two Cys residues, cannot undergo proper glycosylation, which plays an important role in the uptake efficiency of SERT. Herein, we show that the decrease in 5-HT uptake rates of GDM trophoblast is the consequence of defective insulin signaling, which entraps SERT with ERp44 and impairs its glycosylation. In this regard, restoring the normal expression of SERT on the trophoblast surface may represent a novel approach to alleviating some GDM-associated complications.

Published
2014

9. Targeting and crossing of the human maternofetal barrier byListeria monocytogenes: Role of internalin interaction with trophoblast E-cadherin

Author

Michel Huerre, Marc Lecuit, Marie-Cécile Vacher-Lavenu, Jeffrey I. Gordon, D. Michael Nelson, Pascale Cossart, Huot Khun, Steven D. Smith, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Histotechnologie et Pathologie, Institut Pasteur [Paris] (IP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported in part by grants from the Pasteur Institute (to P.C. and M.H.) and National Institutes of Health Grants HD29190 (to D.M.N.) and DK30292 (to J.I.G.). M.L. was the recipient of a European Molecular Biology Organization postdoctoral fellowship. P.C. is an International Research Scholar of the Howard Hughes Medical Institute., Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Washington University in St Louis, CHU Cochin [AP-HP], and DIAKITE, andrée

Subjects
listeria, MESH: Trophoblasts, Placenta, [SDV]Life Sciences [q-bio], MESH: Maternal-Fetal Exchange, Syncytiotrophoblasts, MESH: Listeria monocytogenes, medicine.disease_cause, MESH: Cadherins, MESH: Pregnancy, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Listeriosis, Pregnancy Complications, Infectious, Maternal-Fetal Exchange, MESH: Bacterial Proteins, bactérie, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, LISTERIA MONOCYTOGENES, FETOPLACENTAL LISTERIOSIS, Biological Sciences, Cadherins, MESH: Placenta, Trophoblasts, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, embryonic structures, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, bactérie pathogène, Protein Binding, Secondary infection, Biology, 03 medical and health sciences, Syncytiotrophoblast, Bacterial Proteins, Listeria monocytogenes, E-CADHERIN, medicine, Humans, MESH: Protein Binding, MESH: Pregnancy Complications, Infectious, intéraction, Internalin, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, MESH: Humans, 030306 microbiology, INTERNALIN, Trophoblast, Apical membrane, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, MESH: Listeriosis, MICROBIAL INFECTION STRATEGY, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Listeria monocytogenesproduces severe fetoplacental infections in humans. How it targets and crosses the maternofetal barrier is unknown. We used immunohistochemistry to examine the location ofL. monocytogenesin placental and amniotic tissue samples obtained from women with fetoplacental listeriosis. The results raised the possibility thatL. monocytogenescrosses the maternofetal barrier through the villous syncytiotrophoblast, with secondary infection occurring via the amniotic epithelium. Because epidemiological studies indicate that the bacterial surface protein, internalin (InlA), may play a role in human fetoplacental listeriosis, we investigated the cellular patterns of expression of its host receptor, E-cadherin, at the maternofetal interface. E-cadherin was found on the basal and apical plasma membranes of syncytiotrophoblasts and in villous cytotrophoblasts. Established trophoblastic cell lines, primary trophoblast cultures, and placental villous explants were each exposed to isogenic InlA+ or InlA- strains ofL. monocytogenes,and toL. innocuaexpressing or not InlA. Quantitative assays of cellular invasion demonstrated that bacterial entry into syncytiotrophoblasts occurs via the apical membrane in an InlA–E-cadherin dependent manner. In human placental villous explants, bacterial invasion of the syncytiotrophoblast barrier and underlying villous tissue and subsequent replication produces histopathological lesions that mimic those seen in placentas of women with listeriosis. Thus, the InlA–E-cadherin interaction that plays a key role in the crossing of the intestinal barrier in humans is also exploited byL. monocytogenesto target and cross the placental barrier. Such a ligand–receptor interaction allowing a pathogen to specifically cross the placental villous trophoblast barrier has not been reported previously.

Published
2004

10. Identification of soluble CD146 as a regulator of trophoblast migration: potential role in placental vascular development

Author

Laka Rambeloson, Marcel Blot-Chabaud, Nadia Alfaidy, Alexandrine Bertaud-Foucault, Florence Bretelle, Marie-Dominique Piercecchi-Marti, Elise Kaspi, Benjamin Guillet, Françoise Dignat-George, Nathalie Bardin, Jimmy Stalin, Odile Lacroix, Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Cancer Research, MESH: Rats, Physiology, Angiogenesis, MESH: Trophoblasts, Placenta, Clinical Biochemistry, Enzyme-Linked Immunosorbent Assay, MESH: Flow Cytometry, CD146 Antigen, Biology, Andrology, Vasculogenesis, MESH: Pregnancy, Cell Movement, Pregnancy, medicine, Animals, Humans, MESH: Animals, MESH: Cell Movement, Cells, Cultured, Matrigel, MESH: Humans, Trophoblast, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Fertility, Embryo, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Flow Cytometry, medicine.disease, MESH: Placenta, Rats, Trophoblasts, Fertility, medicine.anatomical_structure, Immunology, CD146, Female, MESH: CD146 Antigen, MESH: Female, MESH: Cells, Cultured
Abstract

International audience; Both vasculogenesis and angiogenesis occur during normal placental vascular development. Additionally, the placenta undergoes a process of vascular mimicry (pseudo-vasculogenesis) where the placental extravillous trophoblast (EVT) that invade the spiral arteries convert from an epithelial to an endothelial phenotype during normal pregnancy. As soluble CD146 (sCD146) constitutes a new physiological factor with angiogenic properties, we hypothesized that it could be involved in the regulation of placental vascular development by acting on EVT. Using placental villous explants, we demonstrated that sCD146 inhibits EVT outgrowth. Consistently, we showed that sCD146 inhibits the ability of EVT cells (HTR8/SVneo) to migrate, invade and form tubes in Matrigel, without affecting their proliferation or apoptosis. The involvement of sCD146 in human pregnancy was investigated by evaluation of sCD146 levels in 50 pregnant women. We observed physiological down-regulation of sCD146 throughout pregnancy. These results prompted us to investigate the effect of prolonged sCD146 administration in a rat model of pregnancy. Repeated systemic sCD146 injections after coupling caused a significant decrease of pregnancy rate and number of embryos. Histological studies performed on placenta evidenced a reduced migration of glycogen cells (analogous to EVT in rat) in sCD146-treated rats. We propose that in human, sCD146 could represent both an attractive biomarker of placental vascular development and a therapeutic target in pregnancy complications associated with pathological angiogenesis.

Published
2014

11. ZO-1 is involved in trophoblastic cell differentiation in human placenta

Author

Danièle Evain-Brion, Graziello Geneau, Michael Grynberg, Jean-Louis Frendo, Diane Carette, Pascale Gerbaud, André Malassiné, Laurent Cronier, Sédami Gnidehou, Jean Guibourdenche, Guillaume Pidoux, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), PremUp Foundation, Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -CHI Créteil-Université Paris Descartes - Paris 5 ( UPD5 ) -Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de physiologie et biologie cellulaires ( IPBC ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Descartes - Paris 5 ( UPD5 ), Caisse d'Assurance Maladie des Professions Libérales Province, Conseil Régional d'Ile de France, INSERM, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Universités-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Small interfering RNA, Time Factors, Physiology, MESH: Trophoblasts, Cellular differentiation, MESH : Immunohistochemistry, Connexin, Chorionic Gonadotropin, MESH : Fluorescence Recovery After Photobleaching, 0302 clinical medicine, MESH: Pregnancy, MESH: Desmoplakins, Pregnancy, MESH: Gestational Age, MESH : Connexin 43, MESH : Female, Cells, Cultured, reproductive and urinary physiology, MESH : Chorionic Gonadotropin, 0303 health sciences, Cell fusion, Tight junction, MESH: Kinetics, Cell Differentiation, MESH : Protein Binding, Zona Occludens-1, MESH: Placenta, Immunohistochemistry, Cell biology, Trophoblasts, medicine.anatomical_structure, Intercellular Junctions, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, MESH : Placenta, 030220 oncology & carcinogenesis, embryonic structures, MESH : Intercellular Junctions, Female, RNA Interference, MESH: Membrane Proteins, MESH : Trophoblasts, MESH : Kinetics, MESH : Cell Differentiation, Fluorescence Recovery After Photobleaching, Protein Binding, MESH: Cells, Cultured, MESH : Time Factors, MESH: Cell Differentiation, trophoblast differentiation, placenta, MESH: RNA Interference, Gestational Age, Biology, MESH: Phosphoproteins, MESH : Immunoprecipitation, Adherens junction, MESH : Desmoplakins, 03 medical and health sciences, MESH: Chorionic Gonadotropin, MESH : Cells, Cultured, medicine, Humans, Immunoprecipitation, MESH: Protein Binding, MESH: Cell Shape, Cell Shape, 030304 developmental biology, MESH: Humans, cell fusion, MESH: Immunoprecipitation, MESH : Cell Fusion, MESH: Time Factors, MESH : Humans, Trophoblast, Membrane Proteins, MESH: Immunohistochemistry, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, Phosphoproteins, MESH: Connexin 43, Kinetics, MESH : Pregnancy, Membrane protein, Desmoplakins, MESH : Membrane Proteins, MESH: Cell Fusion, Connexin 43, Zonula Occludens-1 Protein, MESH : Phosphoproteins, MESH : Cell Shape, MESH : RNA Interference, MESH: Female, MESH: Fluorescence Recovery After Photobleaching, MESH: Intercellular Junctions, MESH : Gestational Age
Abstract

(IF : 4,23); International audience; Trophoblastic cell-cell fusion is an essential event required during human placental development. Several membrane proteins have been described to be directly involved in this process, including connexin 43 (Cx43), syncytin 1 (Herv-W env), and syncytin 2 (Herv-FRD env glycoprotein). Recently, zona occludens (ZO) proteins (peripheral membrane proteins associated with tight junctions, adherens junctions, and gap junctions) were shown to be involved in mouse placental development. Moreover, zona occludens 1 (ZO-1) was localized mainly at the intercellular boundaries between human trophoblastic cells. Therefore the role of ZO-1 in the dynamic process of human trophoblastic cell-cell fusion was investigated using primary trophoblastic cells in culture. In vitro as in situ, ZO-1 was localized mainly at the intercellular boundaries between trophoblastic cells where its expression substantially decreased during differentiation and during fusion. At the same time, Cx43 was localized at the interface of trophoblastic cells and its expression increased during differentiation. To determine a functional role for ZO-1 during trophoblast differentiation, small interfering RNA (siRNA) was used to knock down ZO-1 expression. Cytotrophoblasts treated with ZO-1 siRNA fused poorly, but interestingly, decreased Cx43 expression without altering the functionality of trophoblastic cell-cell communication as measured by relative permeability time constant determined using gap-FRAP experiments. Because kinetics of Cx43 and ZO-1 proteins show a mirror image, a potential association of these two proteins was investigated. By using coimmunoprecipitation experiments, a physical interaction between ZO-1 and Cx43 was demonstrated. These results demonstrate that a decrease in ZO-1 expression reduces human trophoblast cell-cell fusion and differentiation.

Published
2010

12. Coxiella burnetii, the agent of Q fever, replicates within trophoblasts and induces a unique transcriptional response

Author

Christian Capo, Florence Bretelle, J. L. Mege, Yannick Le Priol, Catherine Lepolard, Eric Ghigo, Emmanuel Lemichez, Amira Ben Amara, Suzana P. Salcedo, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'immunologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toxines bactériennes dans la relation hôtes-pathogènes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and Haon, Marie Laure

Subjects
Proteomics, Bacterial Diseases, MESH: Inflammation, MESH: Interleukin-13, Transcription, Genetic, Microarrays, MESH: Trophoblasts, Placenta, lcsh:Medicine, Apoptosis, Mice, Pregnancy, Phagosomes, MESH: Early Growth Response Protein 1, Gram Negative, MESH: Animals, lcsh:Science, reproductive and urinary physiology, Phagosome, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Multidisciplinary, Spectrometric Identification of Proteins, Interleukin-13, biology, Obstetrics and Gynecology, MESH: STAT3 Transcription Factor, 3. Good health, Bacterial Pathogens, Trophoblasts, medicine.anatomical_structure, Infectious Diseases, Phenotype, Coxiella burnetii, Interleukin 13, embryonic structures, Medicine, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, medicine.symptom, Q Fever, Research Article, Q-Fever, STAT3 Transcription Factor, MESH: Q Fever, [SDV.IMM] Life Sciences [q-bio]/Immunology, Inflammation, Q fever, MESH: Phenotype, Microbiology, 03 medical and health sciences, MESH: Gene Expression Profiling, Immune system, MESH: Phagosomes, medicine, Animals, Biology, Microbial Pathogens, MESH: Mice, 030304 developmental biology, Early Growth Response Protein 1, Regulatory Networks, 030306 microbiology, Interleukin-6, Gene Expression Profiling, Macrophages, MESH: Transcription, Genetic, lcsh:R, Immunity, Trophoblast, Computational Biology, Immune Defense, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Virology, MESH: Interleukin-6, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Signaling Networks, MESH: Coxiella burnetii, Pregnancy Complications, MESH: Oligonucleotide Array Sequence Analysis, bacteria, lcsh:Q, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium typically found in myeloid cells. The infection is a source of severe obstetrical complications in humans and cattle and can undergo chronic evolution in a minority of pregnant women. Because C. burnetii is found in the placentas of aborted fetuses, we investigated the possibility that it could infect trophoblasts. Here, we show that C. burnetii infected and replicated in BeWo trophoblasts within phagolysosomes. Using pangenomic microarrays, we found that C. burnetii induced a specific transcriptomic program. This program was associated with the modulation of inflammatory responses that were shared with inflammatory agonists, such as TNF, and more specific responses involving genes related to pregnancy development, including EGR-1 and NDGR1. In addition, C. burnetii stimulated gene networks organized around the IL-6 and IL-13 pathways, which both modulate STAT3. Taken together, these results revealed that trophoblasts represent a protective niche for C. burnetii. The activation program induced by C. burnetii in trophoblasts may allow bacterial replication but seems unable to interfere with the development of normal pregnancy. Such pathophysiologocal processes should require the activation of immune placental cells associated with trophoblasts.

Published
2010

13. A transcriptionally silent RXRalpha supports early embryonic morphogenesis and heart development

Author

Bénédicte Mascrez, Manuel Mark, Pierre Chambon, Norbert B. Ghyselinck, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Peney, Maité

Subjects
Genotype, Transcription, Genetic, Receptors, Retinoic Acid, MESH: Trophoblasts, MESH: Mice, Mutant Strains, Placenta, Mutant, Retinoic acid, Morphogenesis, MESH: Eye, Biology, Retinoid X receptor, Eye, MESH: Genotype, chemistry.chemical_compound, Mice, MESH: Pregnancy, Pregnancy, Embryonic morphogenesis, Animals, MESH: Animals, Receptor, MESH: Mice, Genetics, MESH: Receptors, Retinoic Acid, Multidisciplinary, Retinoic Acid Receptor alpha, MESH: Transcription, Genetic, MESH: Embryo, Mammalian, Heart, Biological Sciences, Embryo, Mammalian, MESH: Placenta, [SDV.ETH] Life Sciences [q-bio]/Ethics, Mice, Mutant Strains, MESH: Morphogenesis, Cell biology, Trophoblasts, [SDV.ETH]Life Sciences [q-bio]/Ethics, MESH: Heart, Nuclear receptor, chemistry, embryonic structures, Eye development, Female, MESH: Female
Abstract

Retinoic acid (RA) receptors (RARs) α, β, and γ heterodimerized with rexinoid receptors (RXRs) α, β, and γ mediate the RA signal. To analyze the contribution of the transcriptional activity of RXRα, the main RXR during embryogenesis, we have engineered a mouse line harboring a transcriptionally silent RXRα mutant that lacks the activation functions AF1 and AF2. All homozygous mutants ( Rxra afo ) display the ocular defects previously observed in compound Rar -null and Rxra / Rar -null mutants, thus demonstrating that a transcriptionally active RXRα is required during eye development. In contrast, the vast majority of Rxra afo fetuses do not display the Rxra -null mutant hypoplasia of the myocardium, thus demonstrating that RXRα can act as a transcriptionally silent heterodimerization partner. Similarly, a transcriptionally silent RXRα mutant can support early embryogenesis, as Rxra afo /Rxrb -null embryos display a normal morphology, contrasting with the severe malformations exhibited by compound Rxra / Rxrb -null embryos. Along the same line, we show that a silent RXRα mutant is sufficient to allow the initial formation of the placental labyrinth, whereas later steps of trophoblast cell differentiation critically requires the AF2, but not the AF1, function of RXRα.

Published
2009

14. Human placental development is impaired by abnormal human chorionic gonadotropin signaling in trisomy 21 pregnancies.: hCG signaling is impaired in trisomy 21 pregnancy

Author

Pidoux, Guillaume, Gerbaud, Pascale, Marpeau, Olivier, Guibourdenche, Jean, Ferreira, Fatima, Badet, Josette, Evain-Brion, Danièle, Frendo, Jean-Louis, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie hormonale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Signal Transduction, endocrine system, MESH: Trophoblasts, MESH : Models, Biological, MESH : Pregnancy Complications, MESH: Pregnancy, MESH: Chorionic Gonadotropin, MESH : Cells, Cultured, MESH: Placentation, MESH : Female, MESH: Receptors, LH, MESH : Placentation, MESH : Receptors, LH, reproductive and urinary physiology, MESH : Chorionic Gonadotropin, MESH : Signal Transduction, MESH: Humans, MESH : Humans, MESH: Models, Biological, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Down Syndrome, MESH : Down Syndrome, MESH : Pregnancy, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, MESH: Pregnancy Complications, MESH : Trophoblasts, MESH: Female, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured
Abstract

International audience; Placental development is markedly abnormal in women bearing a fetus with trisomy 21, with defective syncytiotrophoblast (ST) formation and function. The ST occurs from cytotrophoblast (CT) fusion and plays an essential role by secreting human chorionic gonadotropin (hCG), which is essential to placental development. In trisomy of chromosome 21 (T21) pregnancies, CTs do not fuse and differentiate properly into STs, leading to the secretion of an abnormal and weakly bioactive hCG. In this study we report for the first time, a marked decrease in the number of mature hCG receptor (LH/CG-R) molecules expressed at the surface of T21-affected CTs. The LH/CG-R seems to be functional based on sequencing that revealed no mutations or deletions and binding of recombinant hCG as well as endogenous hCG. We hypothesize that weakly bioactive hCG and lower LH/CG-R expression may be involved in the defect of ST formation. Interestingly, the defective ST formation is mimicked in normal CT cultures by using LH/CG-R small interfering RNA, which result in a lower hCG secretion. Furthermore, treatment of T21-affected CTs with recombinant hCG overcomes in vitro the T21 phenotype, allowing CTs to fuse and form a large ST. These results illustrate for the first time in trisomy 21 pathology, how abnormal endogenous hCG signaling impairs human placental development.

Published
2007

15. Human placental development is impaired by abnormal human chorionic gonadotropin signaling in trisomy 21 pregnancies.: hCG signaling is impaired in trisomy 21 pregnancy

Author

Pidoux, Guillaume, Gerbaud, Pascale, Marpeau, Olivier, Guibourdenche, Jean, Ferreira, Fatima, Badet, Josette, Evain-Brion, Danièle, Frendo, Jean-Louis, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie hormonale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Frendo, Jean-Louis

Subjects
MESH: Signal Transduction, endocrine system, MESH: Humans, MESH: Trophoblasts, MESH: Models, Biological, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Down Syndrome, MESH: Pregnancy, MESH: Chorionic Gonadotropin, MESH: Pregnancy Complications, MESH: Placentation, MESH: Receptors, LH, MESH: Female, hormones, hormone substitutes, and hormone antagonists, reproductive and urinary physiology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, MESH: Cells, Cultured
Abstract

International audience; Placental development is markedly abnormal in women bearing a fetus with trisomy 21, with defective syncytiotrophoblast (ST) formation and function. The ST occurs from cytotrophoblast (CT) fusion and plays an essential role by secreting human chorionic gonadotropin (hCG), which is essential to placental development. In trisomy of chromosome 21 (T21) pregnancies, CTs do not fuse and differentiate properly into STs, leading to the secretion of an abnormal and weakly bioactive hCG. In this study we report for the first time, a marked decrease in the number of mature hCG receptor (LH/CG-R) molecules expressed at the surface of T21-affected CTs. The LH/CG-R seems to be functional based on sequencing that revealed no mutations or deletions and binding of recombinant hCG as well as endogenous hCG. We hypothesize that weakly bioactive hCG and lower LH/CG-R expression may be involved in the defect of ST formation. Interestingly, the defective ST formation is mimicked in normal CT cultures by using LH/CG-R small interfering RNA, which result in a lower hCG secretion. Furthermore, treatment of T21-affected CTs with recombinant hCG overcomes in vitro the T21 phenotype, allowing CTs to fuse and form a large ST. These results illustrate for the first time in trisomy 21 pathology, how abnormal endogenous hCG signaling impairs human placental development.

Published
2007

16. Tracing the glycogen cells with protocadherin 12 during mouse placenta development

Author

Philippe Huber, Christine Rampon, Emmanuelle Tillet, Stéphanie Bouillot, Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Huber, Philippe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
MESH: Trophoblasts, MESH: Glycogen, MESH: Cadherins, MESH: Decidua, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH: Pregnancy, Cell Movement, Pregnancy, MESH: Placentation, Decidual cells, MESH: Animals, MESH: Cell Movement, reproductive and urinary physiology, 0303 health sciences, Glycogen, Decidua, Obstetrics and Gynecology, Cadherins, Cell biology, Trophoblasts, medicine.anatomical_structure, embryonic structures, Female, medicine.medical_specialty, Protocadherin, Mice, Inbred Strains, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Mice, Inbred Strains, MESH: Cell Adhesion, 03 medical and health sciences, Fetal membrane, Placenta, Internal medicine, medicine, Cell Adhesion, Animals, Cell Lineage, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, MESH: Biological Markers, Trophoblast, MESH: Cell Lineage, Embryonic stem cell, Placentation, Protocadherins, Endocrinology, Reproductive Medicine, chemistry, MESH: Female, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

International audience; Among the different trophoblast subtypes of the mouse placenta, the glycogen cells (GC) are one of the trophoblast subtypes that invade the decidua. We previously established that GC specifically expressed protocadherin 12 (PCDH12). In this paper, we investigated the origin of the PCDH12-positive cells and we characterized their fate in the maternal tissues. Our data indicate that they directly originate from the central part of the ectoplacental cone at embryonic day (E) 7.5. PCDH12-positive cells start to accumulate glycogen from E10.5 and the first migrating cells could be observed from this age. Unlike other placental and decidual cells, GC do not express P-cadherin, which may explain their migration properties in this organ. In the decidua, GC settle in the vicinity of the maternal vascular sinuses but do not incorporate in the endothelium. By the end of gestation (E17.5), most GC islets of the decidua enter into a lytic phase and form large lacunae. These lacunae, filled with glycogen, may provide a substantial source of energy at the end of gestation or during delivery. Our data suggest that spongiotrophoblasts and GC are two independent lineages and we bring insights into GC migration and fate.

Published
2006

17. Endothelium, blood vessels and angiogenesis -- a workshop report

Author

Lopa Leach, Guy Whitley, Bill Kalionis, Lynda K. Harris, Rosemary J. Keogh, Josette Badet, Paul Brownbill, Centre for Integrated Systems Biology and Medicine, University of Nottingham, UK (UON), Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Human Development, University of Manchester [Manchester], Division of Basic Medical Sciences, St George's University of London, Department of Perinatal Medicine, Royal Women's Hospital, Action Research, Anatomical Society of Great Britain and Ireland, MRC, INSERM, Lynne Quayle Charitable Trust Fund (Equity Trustees), Marian and EH Flack Trust, Wellcome Trust, Badet, Josette, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Spiral artery, Pathology, Endothelium, Angiogenesis, MESH: Trophoblasts, Chorionic vessels, Placental insufficiency, 030204 cardiovascular system & hematology, Biology, Fas ligand, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Internal medicine, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, MESH: Animals, MESH: Endothelial Cells, MESH: Chorionic Villi, [SDV.BDD]Life Sciences [q-bio]/Development Biology, reproductive and urinary physiology, 030304 developmental biology, 0303 health sciences, spiral artery re-modelling, MESH: Humans, MESH: Vascular Endothelial Growth Factor A, apoptosis, Obstetrics and Gynecology, Trophoblast, homeobox genes, medicine.disease, MESH: Placenta, VEGF, MESH: Gene Expression Regulation, Vascular endothelial growth factor, Endocrinology, medicine.anatomical_structure, Reproductive Medicine, chemistry, embryonic structures, Chorionic villi, MESH: Endothelium, Vascular, angiogenin, MESH: Female, MESH: Neovascularization, Physiologic, Developmental Biology
Abstract

International audience; The aim of this workshop was to discuss in the broadest terms the role of blood vessels in establishing and maintaining a healthy pregnancy. It focused on the vessels at the feto/maternal interface namely the vessels of chorionic villi and the maternal spiral arteries. Cells of these vessels interact closely with trophoblast cells but with very different outcomes. In the chorionic villi this interaction must work to promote and maintain vessel integrity whilst the interactions between the extravillous trophoblasts and the cells of the maternal spiral artery lead in early pregnancy to vessel instability and remodelling and later vessel stabilisation. Knowledge of the mechanisms behind these paradoxical events may allow new therapeutic approaches to pregnancy complications such as placental insufficiency. The specific questions addressed by organisers and participants included the nature of the interaction between the developing chorionic vascular tree and the chorionic villous trophoblast stem cells, the nature of the interaction between extravillous trophoblasts and the cells of the maternal spiral artery specifically whether apoptosis plays a role in the remodelling of maternal spiral arteries. The role of traditional growth factors such as vascular endothelial growth factor (VEGF) in regulation of maternal and fetal vascular growth and vascular tone was also addressed.

Published
2006

18. Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy

Author

Nadia Alfaidy, Pascale Hoffmann, Jean-Jacques Feige, Service gynécologie, obstétrique et médecine de reproduction, CHU Grenoble, Angiogenèse hormono-régulée et angiogenèse tumorale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Feige, Jean-Jacques

Subjects
Vascular Endothelial Growth Factor A, MESH: Trophoblasts, Placenta, MESH: Receptors, G-Protein-Coupled, MESH: Neuropeptides, Receptors, G-Protein-Coupled, chemistry.chemical_compound, MESH: Pregnancy, 0302 clinical medicine, Endocrinology, Pregnancy, MESH: Gastrointestinal Hormones, reproductive and urinary physiology, Cells, Cultured, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Placenta, Prokineticin, Immunohistochemistry, Oxygen tension, Trophoblasts, Vascular endothelial growth factor, medicine.anatomical_structure, embryonic structures, Female, MESH: Pregnancy Trimester, First, MESH: Oxygen, MESH: Cells, Cultured, medicine.medical_specialty, Receptors, Peptide, Blotting, Western, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Gastrointestinal Hormones, 03 medical and health sciences, Internal medicine, medicine, MESH: Blotting, Western, Humans, RNA, Messenger, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: RNA, Messenger, 030304 developmental biology, MESH: Receptors, Peptide, MESH: Humans, Cytotrophoblast, MESH: Vascular Endothelial Growth Factor A, Neuropeptides, Trophoblast, Placentation, MESH: Immunohistochemistry, Prokineticin receptor 1, Oxygen, Pregnancy Trimester, First, MESH: Vascular Endothelial Growth Factor, Endocrine-Gland-Derived, chemistry, Vascular Endothelial Growth Factor, Endocrine-Gland-Derived, MESH: Female
Abstract

International audience; Angiogenesis is a key process of dynamic tissue remodeling occurring during placentation. Compelling evidence indicates that vascular endothelial growth factor (VEGF) is an important mediator of placental angiogenesis and appears to be deregulated in preeclampsia. Recently a new angiogenic factor, endocrine gland-derived VEGF (EG-VEGF), also known as prokineticin 1 (PK1), has been identified, and its expression was shown to be restricted to endocrine glands, including the placenta. In this study we investigated the pattern of expression of EG-VEGF, its related factor Bv8/PK2, and their common receptors, PKR1 and PKR2, in human placenta during the first trimester of pregnancy. We also examined EG-VEGF and PKR1 regulation by oxygen tension in isolated trophoblast cells (TCs). Our results show that EG-VEGF, but not Bv8/PK2, is expressed in human placenta. EG-VEGF is mainly localized to the syncytiotrophoblast layer with the highest expression detected between the 8th and 10th wk of gestation. EG-VEGF expression within placental villi is different from that of VEGF, which is mainly localized in the cytotrophoblast and extravillous trophoblast cells. In TCs, PKR1 mRNA is about 80 times more abundant than PKR2 mRNA. Both EG-VEGF and PKR1 mRNAs appear to be regulated by hypoxia. These findings suggest that EG-VEGF has a direct effect on TCs via its receptor PKR1 and is likely to play an important role in human placentation. The expression pattern of EG-VEGF, its regulation by oxygen tension, and its complementary localization to that of VEGF suggest that this new factor might also be deregulated in preeclampsia.

Published
2005

19. Protocadherin 12 (VE-cadherin 2) is expressed in endothelial, trophoblast, and mesangial cells

Author

Emmanuelle Tillet, Muriel Vernet, Hervé Pointu, Marie-Hélène Prandini, Stéphanie Bouillot, Philippe Huber, Christine Rampon, Ronald Frank, Laboratoire de développement et vieillissement de l'endothélium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Atelier de Transgenèse, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Chemical Biology, German Research Centre for Biotechnology, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Huber, Philippe

Subjects
Male, MESH: Trophoblasts, Cellular differentiation, MESH: Glycogen, MESH: Mice, Knockout, MESH: Cadherins, Mice, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, MESH: Animals, MESH: Endothelial Cells, Mice, Knockout, 0303 health sciences, Cell adhesion molecule, Gene Expression Regulation, Developmental, Cell Differentiation, Cadherins, Glomerular Mesangium, Trophoblasts, medicine.anatomical_structure, MESH: Pluripotent Stem Cells, Female, Glycogen, Pluripotent Stem Cells, MESH: Cell Differentiation, Endothelium, MESH: Glomerular Mesangium, Protocadherin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cell Line, 03 medical and health sciences, medicine, Animals, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, Cadherin, MESH: Biological Markers, Trophoblast, Endothelial Cells, Cell Biology, Embryonic stem cell, Molecular biology, Protocadherins, MESH: Male, MESH: Cell Line, VE-cadherin, MESH: Female, 030217 neurology & neurosurgery, Biomarkers
Abstract

International audience; Protocadherin 12 protein (PCDH12, VE-cadherin 2) is a cell adhesion molecule that has been isolated from endothelial cells. Here, we have used Northern and Western blots, immunohistology, and flow cytometry to examine the distribution of PCDH12 in mouse tissues. It is an N-glycosylated protein of 150-kDa mass. In the endothelium, PCDH12 immunoreactivity was variable and dependent upon the vascular bed. In both the embryo and embryonic stem cell differentiation system, signals were localized in vasculogenic rather than angiogenic endothelium. In addition, the protein was strongly expressed in a subset of invasive cells of the placenta, which were identified as glycogen-rich trophoblasts. In adult mice, strong PCDH12 signals were observed in mesangial cells of kidney glomeruli whereas expression was not detected in other types of perivascular cells. As opposed to most protocadherins, PCDH12 is not expressed in early embryonic (day 12.5) and adult brains. As a first approach to obtain insight into PCDH12 function, we produced transgenic mice deficient in PCDH12, which were viable and fertile. They did not display any obvious histomorphological defects. We conclude that PCDH12 has a unique expression pattern and that its deficiency does not lead to conspicuous abnormalities. Moreover, PCDH12 is the first specific marker for both glycogen-rich trophoblasts and mesangial cells.

Published
2005

20. Developmental expression of the Notch signaling pathway genes during mouse preimplantation development

Author

Sarah Cormier, Michel Cohen-Tannoudji, Sandrine Vandormael-Pournin, Charles Babinet, Biologie du Développement, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), We thank Corinne Chureau-Pommier for providing TS cell total RNAs. This work was funded by the Centre National de la Recherche Scientifique and the Pasteur Institute (GPH 07 Program). Sarah Cormier is recipient of a fellowship from Association de la Recherche contre le Cancer., and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Signal Transduction, Time Factors, MESH: Trophoblasts, Trophoblast stem cells, MESH: Calcium-Binding Proteins, Polymerase Chain Reaction, Mice, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Gene Expression Regulation, Developmental, Inner cell mass, Serrate-Jagged Proteins, MESH: Animals, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics, 0303 health sciences, Receptors, Notch, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Nuclear Proteins, Early mouse development, Trophoblasts, Cell biology, DNA-Binding Proteins, Rbpsuh, Phenotype, medicine.anatomical_structure, Immunoglobulin J Recombination Signal Sequence-Binding Protein, embryonic structures, Intercellular Signaling Peptides and Proteins, Jagged, MESH: Membrane Proteins, Signal Transduction, JAG2, MESH: DNA Primers, JAG1, Embryonic stem cells, MESH: Jagged-1 Protein, Ubiquitin-Protein Ligases, Notch signaling pathway, Deltex, MESH: Stem Cells, Cell fate determination, Biology, MESH: Phenotype, 03 medical and health sciences, MESH: Intracellular Signaling Peptides and Proteins, medicine, MESH: Serrate-Jagged Proteins, Animals, Cell Lineage, RNA, Messenger, Blastocyst, MESH: Intercellular Signaling Peptides and Proteins, Molecular Biology, MESH: Mice, DNA Primers, 030304 developmental biology, MESH: RNA, Messenger, Calcium-Binding Proteins, MESH: Time Factors, Membrane Proteins, Trophoblast, MESH: Polymerase Chain Reaction, MESH: Immunoglobulin J Recombination Signal Sequence-Binding Protein, MESH: Cell Lineage, Embryonic stem cell, MESH: Blastocyst, Notch receptors, Delta-like, MESH: Receptors, Notch, MESH: Nuclear Proteins, Jagged-1 Protein, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins, Developmental Biology
Abstract

3. Note added in proofAfter the present paper was submitted, two whole genome studies on gene expression dynamics during mouse preimplantation development using microarrays were reported (Hamatani et al., and Wang et al., Developmental Cell, (2004), Vol.6, pp. 117–131 and pp. 133–144, respectively). Expression of multiple components of the Notch signaling pathway was demonstrated including three of the genes (Notch3, Dtx2 and Jag2) examined in our study; International audience; Notch signaling is an evolutionary conserved pathway involved in intercellular signaling and essential for proper cell fate choices during development. Thus, it could be involved in mouse preimplantation development where intercellular signaling plays a crucial role, particularly between the inner cell mass and the trophectoderm of the blastocyst. At their face value, the phenotypes observed when disrupting each of the four Notch genes known in the mouse do not support this view as none of them involves perturbation of preimplantation development. However this could be due to functional redundancy and/or maternal expression. As a first step to address this issue, we decided to examine the expression in early development of various genes known to participate in Notch signaling. Here, we report on the expression pattern of Notch1-4, Jagged1 (Jag1), Jag2, Delta-like1 (Dll-1), Dll-3, Dll-4, Rbpsuh, Deltex1(Dtx1)and Dtx2 genes during preimplantation development from unfertilized eggs until late blastocyst stage using a RT-PCR strategy. We show that Notch1, 2, Jag1-2, Dll-3, Rbpsuh and Dtx2 transcripts are expressed at all stages. Notch4 and Dll-4 mRNAs are synthesized from the 2-cell through to the hatched blastocyst stage. Notch3, Dll-1 and Dtx1exhibit a stage dependent expression as their mRNAs are detected in 2-cell embryos and in hatched blastocysts, but are absent or weakly detected at the morula stage. Finally, we show that all the above genes are expressed both in Embryonic and Trophoblast Stem cells (ES and TS cells, respectively). Our results suggest that the Notch pathway may be active during mouse preimplantation development.

Published
2004

21. Angiogenin distribution in human term placenta, and expression by cultured trophoblastic cells

Author

Josette Badet, Danièle Evain-Brion, Yann Bassaglia, Jean-Louis Frendo, Elissavet Hatzi, Nadine Pavlov, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Biological Chemistry, University of Ioannina, Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires (LRCCRRT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), INSERM, Ministère de la Recherche et de la Technologie, Association de la Recherche sur le Cancer, Ligue contre le Cancer, Novo Nordisk Pharmaceutique S.A., Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Centre National de la Recherche Scientifique (CNRS), and Badet, Josette

Subjects
Cancer Research, Physiology, Angiogenesis, MESH: Trophoblasts, MESH : Immunohistochemistry, Placenta, Clinical Biochemistry, MESH: Ribonuclease, Pancreatic, MESH : Ribonuclease, Pancreatic, Gene Expression, MESH : Pregnancy Trimester, Third, MESH : Tissue Distribution, MESH : Fluorescent Antibody Technique, Indirect, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Female, Tissue Distribution, Fluorescent Antibody Technique, Indirect, MESH : Culture Media, Conditioned, Tissue homeostasis, reproductive and urinary physiology, Cells, Cultured, In Situ Hybridization, 0303 health sciences, MESH : Neovascularization, Physiologic, MESH: Culture Media, Conditioned, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Trophoblast, MESH : In Situ Hybridization, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Placenta, MESH : Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Trophoblasts, Endothelial stem cell, Vascular endothelial growth factor, medicine.anatomical_structure, MESH : Placenta, Placental ribonuclease inhibitor, 030220 oncology & carcinogenesis, embryonic structures, MESH: Pregnancy Trimester, Third, Female, MESH : Trophoblasts, MESH: Neovascularization, Physiologic, MESH: Cells, Cultured, MESH: Gene Expression, Angiogenin, Pregnancy Trimester, Third, Neovascularization, Physiologic, Enzyme-Linked Immunosorbent Assay, Biology, Article, 03 medical and health sciences, Syncytiotrophoblast, MESH: In Situ Hybridization, MESH : Cells, Cultured, medicine, MESH: Fluorescent Antibody Technique, Indirect, Humans, MESH: Tissue Distribution, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, MESH: Humans, MESH : Humans, MESH: Biological Markers, MESH: Immunohistochemistry, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Ribonuclease, Pancreatic, Molecular biology, MESH : Biological Markers, MESH : Gene Expression, MESH : Pregnancy, chemistry, Culture Media, Conditioned, MESH: Female, Biomarkers
Abstract

International audience; Human angiogenin is a 14-kDa secreted protein with angiogenic and ribonucleolytic activities. Angiogenin is associated with tumour development but is also present in normal biological fluids and tissues. To further address the physiological role of angiogenin, we studied its expression in situ and in vitro, using the human term placenta as a model of physiological angiogenesis. Angiogenin was immunodetected by light and transmission electron microscopy, and its cellular distribution was established by double immunolabelling with cell markers including von Willebrand factor, platelet/endothelial cell adhesion molecule-1 (PECAM-1), CD34, Tie-2, vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Angiogenin immunoreactivity was detected in villous and extravillous trophoblasts, the trophoblast basement membrane, the endothelial basal lamina, foetal blood vessels, foetal and maternal red blood cells, and amnionic cells. Its expression was confirmed by in situ hybridisation with a digoxygenin-labelled cDNA probe and reverse transcriptase-polymerase chain reaction amplification. Villous cytotrophoblasts, isolated and differentiated in vitro into a functional syncytiotrophoblast, expressed and secreted angiogenin. Given its known biological activities in vitro and its observed pattern of expression, these data suggest that, in human placenta, angiogenin has a role not only in angiogenesis but also in vascular and tissue homeostasis, maternal immune tolerance of the foetus, and host defences.

Published
2004

22. Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy. : hCG and Down Syndrome

Author

Frendo, Jean-Louis, Guibourdenche, Jean, Pidoux, Guillaume, Vidaud, Michel, Luton, Dominique, Giovangrandi, Yves, Porquet, Dominique, Muller, Françoise, Evain-Brion, Danièle, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré - Université Paris Diderot - Paris 7 (UPD7), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5), Service de gynécologie-obstétrique, Service de biochimie, d'hormonologie et de génétique moléculaire, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Ambroise Paré, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
endocrine system, placenta, MESH: Trophoblasts, hCG, MESH: Leydig Cells, MESH: Pregnancy, MESH: Chorionic Gonadotropin, MESH: Fucosyltransferases, MESH: Progesterone, MESH: Antigens, CD, reproductive and urinary physiology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, MESH: RNA, Messenger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Humans, cell fusion, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Down Syndrome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glycosylation, trophoblast, MESH: Male, embryonic structures, MESH: Culture Media, MESH: Female, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured
Abstract

Total human chorionic gonadotropin (hCG) is high in maternal serum at 14-18 wk of trisomy 21 (T21)-affected pregnancy, despite low placental hCG synthesis. We sought an explanation for this paradox. We first observed that, in T21-affected pregnancies, maternal serum hCG levels peaked at around 10 wk and then followed the same pattern throughout pregnancy as in controls, albeit at a higher (2.2-fold) level. After delivery, hCG clearance was not significantly different from that in controls. We isolated cytotrophoblasts from 29 T21-affected placentas (12-25 wk) and 13 gestational age-matched control placentas and cultured them for 3 d. In this large series, we confirmed that, in the culture medium of trophoblasts isolated from T21 placentas, hCG secretion was significantly lower (P < 0.003) than in controls, in contrast to the high hCG in maternal serum of the same patients. In T21 cultured trophoblasts, transcripts of sialyltransferase-1 and fucosyltransferase-1 were abnormally high. In corresponding culture medium, hCG was abnormally glycosylated; highly acidic [isoelectric points (pHi) = 4.5] as shown by isoelectric focusing, immunoblotting, and lectin binding; and weakly bioactive (46% of control) as determined using the Leydig cell model. In conclusion, T21 trophoblast cells produced hCG that was weakly bioactive and abnormally glycosylated but whose maternal clearance was unaltered.

Published
2004

23. Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy.: hCG and Down Syndrome

Author

Frendo, Jean-Louis, Guibourdenche, Jean, Pidoux, Guillaume, Vidaud, Michel, Luton, Dominique, Giovangrandi, Yves, Porquet, Dominique, Muller, Françoise, Evain-Brion, Danièle, Frendo, Jean-Louis, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5), Service de gynécologie-obstétrique, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP]

Subjects
endocrine system, placenta, MESH: Trophoblasts, hCG, MESH: Leydig Cells, MESH: Pregnancy, MESH: Chorionic Gonadotropin, MESH: Fucosyltransferases, MESH: Progesterone, MESH: Antigens, CD, reproductive and urinary physiology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, MESH: RNA, Messenger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, cell fusion, MESH: Humans, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Down Syndrome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glycosylation, trophoblast, MESH: Male, embryonic structures, MESH: Culture Media, MESH: Female, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured
Abstract

Total human chorionic gonadotropin (hCG) is high in maternal serum at 14-18 wk of trisomy 21 (T21)-affected pregnancy, despite low placental hCG synthesis. We sought an explanation for this paradox. We first observed that, in T21-affected pregnancies, maternal serum hCG levels peaked at around 10 wk and then followed the same pattern throughout pregnancy as in controls, albeit at a higher (2.2-fold) level. After delivery, hCG clearance was not significantly different from that in controls. We isolated cytotrophoblasts from 29 T21-affected placentas (12-25 wk) and 13 gestational age-matched control placentas and cultured them for 3 d. In this large series, we confirmed that, in the culture medium of trophoblasts isolated from T21 placentas, hCG secretion was significantly lower (P < 0.003) than in controls, in contrast to the high hCG in maternal serum of the same patients. In T21 cultured trophoblasts, transcripts of sialyltransferase-1 and fucosyltransferase-1 were abnormally high. In corresponding culture medium, hCG was abnormally glycosylated; highly acidic [isoelectric points (pHi) = 4.5] as shown by isoelectric focusing, immunoblotting, and lectin binding; and weakly bioactive (46% of control) as determined using the Leydig cell model. In conclusion, T21 trophoblast cells produced hCG that was weakly bioactive and abnormally glycosylated but whose maternal clearance was unaltered.

Published
2004

24. Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation

Author

Frendo, Jean-Louis, Olivier, Delphine, Cheynet, Valérie, Blond, Jean-Luc, Bouton, Olivier, Vidaud, Michel, Rabreau, Michèle, Evain-Brion, Danièle, Mallet, François, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Système macromoléculaires et mmunovirologie humaine, IFR128-bioMérieux SA-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5), Institut d'histocytologie, Université Sciences et Technologies - Bordeaux 1 (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1, Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), and IFR128 - bioMérieux SA - Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Cell Differentiation, MESH: Humans, MESH: Immunoblotting, MESH: Trophoblasts, viruses, MESH: Time Factors, MESH: Immunohistochemistry, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Giant Cells, MESH: Oligonucleotides, Antisense, MESH: RNA, MESH: Gene Products, env, MESH: Oligonucleotides, MESH: Cell Fusion, embryonic structures, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, reproductive and urinary physiology, MESH: Endogenous Retroviruses, MESH: RNA, Messenger
Abstract

We recently demonstrated that the product of the HERV-W env gene, a retroviral envelope protein also dubbed syncytin, is a highly fusogenic membrane glycoprotein inducing the formation of syncytia on interaction with the type D mammalian retrovirus receptor. In addition, the detection of HERV-W Env protein (Env-W) expression in placental tissue sections led us to propose a role for this fusogenic glycoprotein in placenta formation. To evaluate this hypothesis, we analyzed the involvement of Env-W in the differentiation of primary cultures of human villous cytotrophoblasts that spontaneously differentiate by cell fusion into syncytiotrophoblasts in vitro. First, we observed that HERV-W env mRNA and glycoprotein expression are colinear with primary cytotrophoblast differentiation and with expression of human chorionic gonadotropin (hCG), a marker of syncytiotrophoblast formation. Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression. Finally, by using specific antisense oligonucleotides, we demonstrated that inhibition of Env-W protein expression leads to a decrease of trophoblast fusion and differentiation, with the secretion of hCG in culture medium of antisense oligonucleotide-treated cells being decreased by fivefold. Taken together, these results strongly support a direct role for Env-W in human trophoblast cell fusion and differentiation.

Published
2003

25. Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation.: HERV-W Env GLYCOPROTEIN IN TROPHOBLAST DIFFERENTIATION

Author

Frendo, Jean-Louis, Olivier, Delphine, Cheynet, Valérie, Blond, Jean-Luc, Bouton, Olivier, Vidaud, Michel, Rabreau, Michèle, Evain-Brion, Danièle, Mallet, François, Frendo, Jean-Louis, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Système macromoléculaires et mmunovirologie humaine, IFR128-bioMérieux SA-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5), Institut d'histocytologie, and Université Sciences et Technologies - Bordeaux 1 (UB)

Subjects
MESH: Cell Differentiation, MESH: Humans, MESH: Immunoblotting, MESH: Trophoblasts, viruses, MESH: Time Factors, MESH: Immunohistochemistry, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Giant Cells, MESH: Oligonucleotides, Antisense, MESH: RNA, MESH: Gene Products, env, MESH: Oligonucleotides, MESH: Cell Fusion, embryonic structures, reproductive and urinary physiology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, MESH: Endogenous Retroviruses, MESH: RNA, Messenger
Abstract

We recently demonstrated that the product of the HERV-W env gene, a retroviral envelope protein also dubbed syncytin, is a highly fusogenic membrane glycoprotein inducing the formation of syncytia on interaction with the type D mammalian retrovirus receptor. In addition, the detection of HERV-W Env protein (Env-W) expression in placental tissue sections led us to propose a role for this fusogenic glycoprotein in placenta formation. To evaluate this hypothesis, we analyzed the involvement of Env-W in the differentiation of primary cultures of human villous cytotrophoblasts that spontaneously differentiate by cell fusion into syncytiotrophoblasts in vitro. First, we observed that HERV-W env mRNA and glycoprotein expression are colinear with primary cytotrophoblast differentiation and with expression of human chorionic gonadotropin (hCG), a marker of syncytiotrophoblast formation. Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression. Finally, by using specific antisense oligonucleotides, we demonstrated that inhibition of Env-W protein expression leads to a decrease of trophoblast fusion and differentiation, with the secretion of hCG in culture medium of antisense oligonucleotide-treated cells being decreased by fivefold. Taken together, these results strongly support a direct role for Env-W in human trophoblast cell fusion and differentiation.

Published
2003

26. Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome.: TROPHOBLAST AND DOWNS SYNDROME

Author

Frendo, Jean-Louis, Vidaud, Michel, Guibourdenche, Jean, Luton, Dominique, Muller, Françoise, Bellet, Dominique, Giovagrandi, Yves, Couturier-Tarrade, Anne, Porquet, Dominique, Blot, Philippe, Evain-Brion, Danièle, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de gynécologie-obstétrique, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré - Université Paris Diderot - Paris 7 (UPD7), Service de biochimie, d'hormonologie et de génétique moléculaire, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Ambroise Paré, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
MESH: Cell Differentiation, MESH: Humans, MESH: Immunoblotting, MESH: Trophoblasts, MESH: Adult, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Down Syndrome, MESH: Placenta, MESH: Giant Cells, MESH: Pregnancy, MESH: Hormones, MESH: RNA, MESH: Reverse Transcriptase Polymerase Chain Reaction, embryonic structures, MESH: Endocrine Glands, MESH: Proteins, MESH: Female, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, reproductive and urinary physiology, MESH: Cells, Cultured
Abstract

The syncytiotrophoblast (ST) is one of the major components of the human placenta, as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. The aim of this study was to elucidate the formation and function of the ST in trisomy 21 (Down's syndrome). We first used the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblasts were isolated from 15 trisomy 21-affected placentas (12-35 weeks gestation) and 10 gestational age-matched control placentas. In vitro cytotrophoblasts isolated from normal placenta fused to form the ST. This was associated with an increase in transcript levels and in the secretion of hCG, human placental lactogen, placental GH, and leptin. In trisomy 21-affected placentas, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of these hormones compared to those in cultured cells isolated from control age-matched placentas. These results were confirmed by a significant (P < 0.001) decrease in gene expression in total homogenates of trisomy 21-affected placentas compared to controls. These results will be of help in understanding the maternal hormonal markers of fetal trisomy 21 and the consequences of placental defects for fetal development.

Published
2000

27. Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome

Author

Frendo, Jean-Louis, Vidaud, Michel, Guibourdenche, Jean, Luton, Dominique, Muller, Françoise, Bellet, Dominique, Giovagrandi, Yves, Couturier-Tarrade, Anne, Porquet, Dominique, Blot, Philippe, Evain-Brion, Danièle, Frendo, Jean-Louis, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de gynécologie-obstétrique, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP]

Subjects
MESH: Cell Differentiation, MESH: Humans, MESH: Immunoblotting, MESH: Trophoblasts, MESH: Adult, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Down Syndrome, MESH: Placenta, MESH: Giant Cells, MESH: Pregnancy, MESH: Hormones, MESH: RNA, MESH: Reverse Transcriptase Polymerase Chain Reaction, embryonic structures, MESH: Endocrine Glands, MESH: Proteins, MESH: Female, reproductive and urinary physiology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, MESH: Cells, Cultured
Abstract

The syncytiotrophoblast (ST) is one of the major components of the human placenta, as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. The aim of this study was to elucidate the formation and function of the ST in trisomy 21 (Down's syndrome). We first used the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblasts were isolated from 15 trisomy 21-affected placentas (12-35 weeks gestation) and 10 gestational age-matched control placentas. In vitro cytotrophoblasts isolated from normal placenta fused to form the ST. This was associated with an increase in transcript levels and in the secretion of hCG, human placental lactogen, placental GH, and leptin. In trisomy 21-affected placentas, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of these hormones compared to those in cultured cells isolated from control age-matched placentas. These results were confirmed by a significant (P < 0.001) decrease in gene expression in total homogenates of trisomy 21-affected placentas compared to controls. These results will be of help in understanding the maternal hormonal markers of fetal trisomy 21 and the consequences of placental defects for fetal development.

Published
2000

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