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1. Effects of Acute Dengue Infection on Sperm and Virus Clearance in Body Fluids of Men

Author

Mons, Joffrey, Mahe-Poiron, Dominique, Mansuy, Jean-Michel, Lheureux, Helene, Nigon, Delphine, Moinard, Nathalie, Hamdi, Safouane, Pasquier, Christophe, Dejucq-Rainsford, Nathalie, and Bujan, Louis

Subjects
Dengue -- Complications and side effects, Body fluids -- Composition -- Health aspects, Spermatozoa -- Health aspects -- Composition, Host-virus relationships -- Health aspects -- Physiological aspects, Health
Abstract

Dengue is a mosquitoborne viral disease common in regions with tropical climates. Worldwide annual dengue incidence is estimated at [approximately equal to]100 million diagnosed and [approximately equal to]300 million asymptomatic [...]

Published
2022
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5. Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection

Author

Camus, Céline, Matusali, Giulia, Bourry, Olivier, Mahe, Dominique, Aubry, Florence, Bujan, Louis, Pasquier, Christophe, Massip, Patrice, Ravel, Célia, Zirafi, Onofrio, Munch, Jan, Roan, Nadia R, Pineau, Charles, and Dejucq-Rainsford, Nathalie

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Clinical Research, HIV/AIDS, Sexually Transmitted Infections, 2.1 Biological and endogenous factors, Aetiology, Infection, CD4-Positive T-Lymphocytes, Cells, Cultured, HIV Infections, Humans, Leukocytes, Mononuclear, Male, Semen, CCR5, cytokines, enhancing peptides, HIV-1, infected men, receptors, semen, transmission, RANTES/CCL5, CD4(+) T cells, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

ObjectivesSemen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors.DesignWe compared the effect of seminal plasma (SP) from chronically HIV-infected (SP+) versus uninfected donors (SP-) on HIV-1 infection of peripheral blood mononuclear cells (PBMCs) and CD4 T cells.MethodsPrimary cells were infected with HIV-1 in the presence of SP+ or SP- and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP- were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels.ResultsSP- efficiently enhanced HIV-1 R5 infection of CD4 T cells, whereas SP+ enhancing activity was significantly reduced. RANTES (CCL5) concentrations were elevated in SP+ relative to SP-, whereas the concentrations of infectivity-enhancing peptides [semen-derived enhancer of viral infection (SEVI), SEM1, SEM2] were similar. CCR5 membrane expression levels were reduced on CD4 T cells shortly postexposure to SP+ compared with SP- and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands' concentrations in semen. SP+ and SP- displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES (regulated on activation, normal T-cell expressed and secreted) from SPs modulated their effect on PBMC infection by R5-tropic HIV-1.ConclusionSemen from HIV-infected donors exhibits a significantly reduced enhancing potential on CD4 T-cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV-infected men can influence the ability of semen to enhance infection.

Published
2016

6. SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo

Author

Mahé, Dominique, primary, Bourgeau, Salomé, additional, da Silva, Janaina, additional, Schlederer, Julie, additional, Satie, Anne-Pascale, additional, Kuassivi, Nadège, additional, Mathieu, Romain, additional, Guillou, Yves-Marie, additional, Le Tortorec, Anna, additional, Guivel-Benhassine, Florence, additional, Schwartz, Olivier, additional, Plotton, Ingrid, additional, and Dejucq-Rainsford, Nathalie, additional

Published
2023
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7. Sperm DNA methylation dynamics after chemotherapy: a longitudinal study of a patient with testicular germ cell tumor treatment.

Author

Neyroud, Anne‐Sophie, Rolland, Antoine Dominique, Lecuyer, Gwendoline, Evrard, Bertrand, Alary, Nathan, Dejucq‐Rainsford, Nathalie, Bujan, Louis, Ravel, Célia, and Chalmel, Frédéric

Subjects
DNA methylation, TUMOR treatment, MALE infertility, GERM cell tumors, SPERMATOZOA, CANCER chemotherapy, LONGITUDINAL method
Abstract

Background: An important issue for young men affected by testicular germ cell tumor (TGCT) is how TGCT and its treatment will affect, transiently or permanently, their future reproductive health. Previous studies have reported that xenobiotics can induce changes on human sperm epigenome and have the potential to promote epigenetic alterations in the offspring. Objectives: Here, we report the first longitudinal DNA methylation profiling of frozen sperm from a TGCT patient before and up to 2 years after a bleomycin, etoposide, and cisplatin (BEP) chemotherapy. Materials and methods: A TGCT was diagnosed in a 30‐year‐old patient. A cryopreservation of spermatozoa was proposed before adjuvant BEP treatment. Semen samples were collected before and after chemotherapy at 6, 9, 12, and 24 months. The DNA methylation status was determined by RRBS to detect DNA differentially methylated regions (DMRs). Results: The analysis revealed that among the 74 DMRs showing modified methylation status 6 months after therapy, 17 remained altered 24 months after treatment. We next associated DMRs with differentially methylated genes (DMGs), which were subsequently intersected with loci known to be important or expressed during early development. Discussion and conclusion: The consequences of the cancer treatment on the sperm epigenome during the recovery periods are topical issues of increasing significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. The altered methylated status of these DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis, potentially leading to developmental disorders or miscarriages. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Chikungunya Virus replicates in the human testis and transiently decreases testosterone production in infected men

Author

Ciesielski, Vincent, additional, Cartron, Matéo, additional, Houzet, Laurent, additional, Kuassivi, Nadège O., additional, Abiven, Hervé, additional, Guillou, Yves-Marie, additional, Roques, Pierre, additional, Cabié, André, additional, Plotton, Ingrid, additional, Mahé-Poiron, Dominique, additional, and Dejucq-Rainsford, Nathalie, additional

Published
2023
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10. Zika virus infects human testicular tissue and germ cells

Author

Matusali, Giulia, Houzet, Laurent, Satie, Anne-Pascale, Mahe, Dominique, Aubry, Florence, Couderc, Therese, Frouard, Julie, Bourgeau, Salome, Bensalah, Karim, Lavoue, Sylvain, Joguet, Guillaume, Bujan, Louis, Cabie, Andre, Avelar, Gleide, Lecuit, Marc, Le Tortorec, Anna, and Dejucq-Rainsford, Nathalie

Subjects
Host-virus relationships, Semen -- Properties, Testis -- Physiological aspects, Zika virus -- Health aspects, Health care industry
Abstract

Zika virus (ZIKV) is a teratogenic mosquito-borne flavivirus that can be sexually transmitted from man to woman. The finding of high viral loads and prolonged viral shedding in semen suggests that ZIKV replicates within the human male genital tract, but its target organs are unknown. Using ex vivo infection of organotypic cultures, we demonstrated here that ZIKV replicates in human testicular tissue and infects a broad range of cell types, including germ cells, which we also identified as infected in semen from ZIKV-infected donors. ZIKV had no major deleterious effect on the morphology and hormonal production of the human testis explants. Infection induced a broad antiviral response but no IFN upregulation and minimal proinflammatory response in testis explants, with no cytopathic effect. Finally, we studied ZIKV infection in mouse testis and compared it to human infection. This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents., Introduction Zika virus (ZIKV) is a teratogenic arthropod-borne flavivirus that recently emerged in the Pacific Islands (2007), Oceania (2013), and the Americas (2015). While ZIKV's primary mode of transmission is [...]

Published
2018
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12. Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI

Author

Kim, Kyeong-Ae, Yolamanova, Maral, Zirafi, Onofrio, Roan, Nadia R, Staendker, Ludger, Forssmann, Wolf-Georg, Burgener, Adam, Dejucq-Rainsford, Nathalie, Hahn, Beatrice H, Shaw, George M, Greene, Warner C, Kirchhoff, Frank, and Münch, Jan

Abstract

Abstract Background HIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial. Results Here, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen-mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI. Conclusions Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy.

Published
2010

13. The Acute Exposure of Human Adult Testis Tissue to Cannabinoids THC and CBD Does Not Impact Testosterone Production Nor Germ Cell Lineage.

Author

da Silva, Janaina, Dochez-Arnault, Juliette, Desdoits-Lethimonier, Chritèle, Dejucq-Rainsford, Nathalie, and Gely-Pernot, Aurore

Subjects
CANNABINOIDS, TETRAHYDROCANNABINOL, LEYDIG cells, MESSENGER RNA
Abstract

Purpose: While an increased risk of developing germ cell tumors has been established in regular cannabis consumers, there is conflicting evidence about an association between cannabis use and testosterone levels in those regular consumers. In this context, we aimed to determine whether Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the two major and beststudied cannabinoids present in cannabis, also the most used for therapeutic applications, can directly impact the steroidogenic function and germ cell lineage of the human adult testis. Materials and Methods: We used our well-characterized organotypic culture of human testis, in which adult testis explants were exposed to CBD, THC, or CBD/THC [ratio 1:1] from 10-9 to 10-5 M for up to either 48 hours or 9 days of culture. The testes were obtained from multi-organ donors (n=13; mean age: 55.15±5.62 y). Results: The testosterone production and the spatial distribution of Leydig cells did not change upon CBD and/or THC exposure versus controls after 48 hours or 9 days. The overall tissue morphology of the cannabinoids-exposed testis explants was similar to their control upon 24 hours or 9 days of exposure, a finding confirmed by morphometric analyses on short-term cultures. In line, the number of apoptotic cells was not affected by either 48 hours or 9 days of cannabinoids treatment versus mock. Cannabinoids had no impact on the number of proliferating cells nor on mRNA expression of genes encoding proteins involved in germ cell differentiation, meiosis, or Sertoli and Leydig functions after 24 hours exposure. Conclusions: Altogether, these findings show an absence of acute direct effects of exposure to cannabis-derived cannabinoids THC and CBD on testicular testosterone production and germ cells ex vivo. Further studies are warranted to explore an indirect impact of cannabinoids on testis functions through the hypothalamic-pituitary-testis axis, as well as the potential effects of long-term exposures. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Minimal change nephrotic syndrome in patients infected with human immunodeficiency virus: a retrospective study of 8 cases

Author

ARRESTIER, Romain, SATIE, Anne-Pascale, ZHANG, Shao-yu, PLAISIER, Emmanuelle, ISNARD-BAGNIS, Corinne, GATAULT, Philippe, RAIMBOURG, Quentin, BUOB, David, VOCILA, Flavia, HENG, Anne-Elisabeth, FRANCOIS, Helene, MOKTEFI, Anissa, CANAUD, Guillaume, MATIGNON, Marie, DEJUCQ-RAINSFORD, Nathalie, BROCHERIOU, Isabelle, SAHALI, Dil, and AUDARD, Vincent

Published
2018
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20. Viral persistence and innate immunity in the male genital tract: a tale of two viruses

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Dejucq-Rainsford, Nathalie

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

21. Viral persistence in the male genital tract: a tale of two viruses

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dejucq-Rainsford, Nathalie, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

22. Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis

Author

Leverrier‐Penna, Sabrina, primary, Michel, Alain, additional, Lecante, Laetitia L., additional, Costet, Nathalie, additional, Suglia, Antonio, additional, Desdoits‐Lethimonier, Christèle, additional, Boulay, Hugoline, additional, Viel, Roselyne, additional, Chemouny, Jonathan M., additional, Becker, Emmanuelle, additional, Lavoué, Vincent, additional, Rolland, Antoine D., additional, Dejucq‐Rainsford, Nathalie, additional, Vigneau, Cécile, additional, and Mazaud‐Guittot, Séverine, additional

Published
2021
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23. Human Ubiquitin-Specific Peptidase 18 Is Regulated by microRNAs via the 3'Untranslated Region, A Sequence Duplicated in Long Intergenic Non-coding RNA Genes Residing in chr22q11.21

Author

Rubino, Erminia, Cruciani, Melania, Tchitchek, Nicolas, Le Tortorec, Anna, ROLLAND, Antoine, Veli, Önay, Vallet, Leslie, Gaggi, Giulia, Michel, Frédérique, Dejucq-Rainsford, Nathalie, Pellegrini, Sandra, Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Research in the Unit of Cytokine Signaling is funded by the Institut Pasteur, the Fondation pour la Recherche Médicale (Equipe FRM DEQ20170336741) and the Institut National de la Santé et de la Recherche Médicale (Inserm). ER was supported by Sorbonne Université and by FRM. MC was supported by the FRM grant above. GG and ÖV were supported by the Erasmus plus programme of the EU commission. Work at Rennes University is funded by Inserm and Défis Scientifiques Emergents., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Gestionnaire, HAL Sorbonne Université 5

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 22q11.2, 3'untranslated region, microRNAs, microRNAs, ubiquitin-specific peptidase, Testis, Genetics, Molecular Medicine, type I interferon, long intergenic non-coding RNA, 3'untranslated region, Genetics (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Original Research
Abstract

International audience; Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of IFN-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here, we identified microRNAs (miRNAs) that efficiently target USP18 through binding to the 3’untranslated region (3’UTR). Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baseline USP18. Intriguingly, the USP18 3’UTR sequence is duplicated in human and chimpanzee genomes. In humans, four USP18 3’UTR copies were previously found to be embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and known as FAM247A-D. Here, we further characterized their sequence and measured their expression profile in human tissues. Importantly, we describe an additional lincRNA bearing USP18 3’UTR (here linc-UR-B1) that is expressed only in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation between linc-UR-B1 and USP18 expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.

Published
2021

27. Antiviral immunity and male genital tract infections: a tale of two viruses

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dejucq-Rainsford, Nathalie, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

28. Le VIH-1, un lentivirus au potentiel d’endogénisation dans la lignée germinale humaine ?

Author

Mahé, Dominique, Matusali, G, Deleage, C, Alvarenga, R, Satie, A.-P, Pagliuzza, A, Mathieu, R, Lavoué, S, Jégou, B, Chomont, N, de França, L.R, Houzet, L, Rolland, Antoine D., Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Basic Research Laboratory [Frederick, MD, USA] (NIH/NCI), Frederick National Laboratory for Cancer Research (FNLCR)-Leidos Biomedical Research, Inc [Frederick, MD, USA], Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Lentivirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, VIH-1, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2020

29. Mécanismes moléculaires de la persistance virale dans le testicule humain : rôle de la réponse immunitaire innée

Author

Kuassivi, N, Aubry, F., Houzet, L, Satie, A-P, Mahé, D, Lavoue, S., Mathieu, R., Le Tortorec, Anna, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and MAHE, Dominique

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

30. Endocrine disruption in human fetal testis explants by individual and combined exposures to selected pharmaceuticals, pesticides, and environmental pollutants

Author

Gaudriault, Pierre, Mazaud-Guittot, Severine, Lavoue, Vincent, Coiffec, Isabelle, Lesne, Laurianne, Dejucq-Rainsford, Nathalie, Scholze, Martin, Kortenkamp, Andreas, and Jegou, Bernard

Subjects
Pesticides -- Health aspects, Endocrine disruptors -- Health aspects, Male genital diseases -- Risk factors, Pollutants -- Health aspects, Prenatal influences -- Health aspects, Pharmacokinetics -- Health aspects, Environmental issues, Health
Abstract

Background: Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. Objectives: Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals. Methods: We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures. Results: We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight. Conclusions: Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014, Introduction In chemical hazard characterizations for pesticides, biocides, and other potentially toxic chemicals, single substances are tested in relevant animal studies with the aim of estimating exposures that are without [...]

Published
2017
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32. Potential for Virus Endogenization in Humans through Testicular Germ Cell Infection: the Case of HIV

Author

Mahé, Dominique, primary, Matusali, Giulia, additional, Deleage, Claire, additional, Alvarenga, Raquel L. L. S., additional, Satie, Anne-Pascale, additional, Pagliuzza, Amélie, additional, Mathieu, Romain, additional, Lavoué, Sylvain, additional, Jégou, Bernard, additional, de França, Luiz R., additional, Chomont, Nicolas, additional, Houzet, Laurent, additional, Rolland, Antoine D., additional, and Dejucq-Rainsford, Nathalie, additional

Published
2020
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33. New insights into the genetic basis of premature ovarian insufficiency: Novel causative variants and candidate genes revealed by genomic sequencing

Author

Jaillard, Sylvie, primary, Bell, Katrina, additional, Akloul, Linda, additional, Walton, Kelly, additional, McElreavy, Kenneth, additional, Stocker, William A., additional, Beaumont, Marion, additional, Harrisson, Craig, additional, Jääskeläinen, Tiina, additional, Palvimo, Jorma J., additional, Robevska, Gorjana, additional, Launay, Erika, additional, Satié, Anne-Pascale, additional, Listyasari, Nurin, additional, Bendavid, Claude, additional, Sreenivasan, Rajini, additional, Duros, Solène, additional, van den Bergen, Jocelyn, additional, Henry, Catherine, additional, Domin-Bernhard, Mathilde, additional, Cornevin, Laurence, additional, Dejucq-Rainsford, Nathalie, additional, Belaud-Rotureau, Marc-Antoine, additional, Odent, Sylvie, additional, Ayers, Katie L., additional, Ravel, Célia, additional, Tucker, Elena J., additional, and Sinclair, Andrew H., additional

Published
2020
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34. Human USP18 is regulated by miRNAsviathe 3’UTR, a sequence duplicated in lincRNA genes residing in chr22q11.21

Author

Rubino, Erminia, primary, Cruciani, Melania, additional, Tchitchek, Nicolas, additional, Le Tortorec, Anna, additional, Rolland, Antoine D., additional, Veli, Önay, additional, Vallet, Leslie, additional, Gaggi, Giulia, additional, Michel, Frédérique, additional, Dejucq-Rainsford, Nathalie, additional, and Pellegrini, Sandra, additional

Published
2020
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36. Zika virus infects the human testis

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Dejucq-Rainsford, Nathalie

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

37. Transmission du VIH-1 associée aux cellules à travers la muqueuse colorectale ex vivo et modulation par le liquide séminal

Author

Frouard, J., Matusali, G, Satie, Ap, Valentin, R., Sulpice, L., Ravel, C., Rioux-Leclercq, N., Le Tortorec, Anna, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dejucq-Rainsford, Nathalie

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2018

38. Zika virus infection of the human male genital tract

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dejucq-Rainsford, Nathalie, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV] Life Sciences [q-bio], [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV]Life Sciences [q-bio], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

39. RNA profiling of human testicular cells identifies syntenic lncRNAs associated with spermatogenesis

Author

Rolland, Antoine D., Evrard, B, Darde, T A, Le Béguec, C, Le Bras, Y, Bensalah, K, Lavoué, S, Jost, B, Primig, M, Dejucq-Rainsford, Nathalie, Chalmel, F, Jégou, Bernard, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), CHU Pontchaillou [Rennes], 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), EHESP-Irset (EHESP-Irset), Rennes Métropole ‘Défis Scientifiques Émergents’, N 10028NN, INERIS-STORM, l’Ecole des Hautes Études en Santé Publique, l’Université de Rennes 1, and l’Institut National de la Santé et de la Recherche Médicale

Subjects
[SDV]Life Sciences [q-bio], Novel unannotated transcripts, Human spermatogenesis, Long non-coding RNAs, RNA profiling, Synteny, Expression conservation
Abstract

International audience; STUDY QUESTIONIs the noncoding transcriptional landscape during spermatogenesis conserved between human and rodents?SUMMARY ANSWERWe identified a core group of 113 long noncoding RNAs (lncRNAs) and 20 novel genes dynamically and syntenically transcribed during spermatogenesis.WHAT IS KNOWN ALREADYSpermatogenesis is a complex differentiation process driven by a tightly regulated and highly specific gene expression program. Recently, several studies in various species have established that a large proportion of known lncRNAs are preferentially expressed during meiosis and spermiogenesis in a testis-specific manner.STUDY DESIGN, SIZE, DURATIONTo further investigate lncRNA expression in human spermatogenesis, we carried out a cross-species RNA profiling study using isolated testicular cells.PARTICIPANTS/MATERIALS, SETTING, METHODSHuman testes were obtained from post-mortem donors (N = 8, 51 years old on average) or from prostate cancer patients with no hormonal treatment (N = 9, 80 years old on average) and only patients with full spermatogenesis were used to prepare enriched populations of spermatocytes, spermatids, Leydig cells, peritubular cells and Sertoli cells. To minimize potential biases linked to inter-patient variations, RNAs from two or three donors were pooled prior to RNA-sequencing (paired-end, strand-specific). Resulting reads were mapped to the human genome, allowing for assembly and quantification of corresponding transcripts.MAIN RESULTS AND THE ROLE OF CHANCEOur RNA-sequencing analysis of pools of isolated human testicular cells enabled us to reconstruct over 25 000 transcripts. Among them we identified thousands of lncRNAs, as well as many previously unidentified genes (novel unannotated transcripts) that share many properties of lncRNAs. Of note is that although noncoding genes showed much lower synteny than protein-coding ones, a significant fraction of syntenic lncRNAs displayed conserved expression during spermatogenesis.LARGE SCALE DATARaw data files (fastq) and a searchable table (.xlss) containing information on genomic features and expression data for all refined transcripts have been submitted to the NCBI Gene Expression Omnibus under accession number GSE74896.LIMITATIONS, REASONS FOR CAUTIONIsolation procedures may alter the physiological state of testicular cells, especially for somatic cells, leading to substantial changes at the transcriptome level. We therefore cross-validated our findings with three previously published transcriptomic analyses of human spermatogenesis. Despite the use of stringent filtration criteria, i.e. expression cut-off of at least three fragments per kilobase of exon model per million reads mapped, fold-change of at least three and false discovery rate adjusted P-values of less than

Published
2019

42. Modulation of HIV cell free and cell associated infection by seminal plasma

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Dejucq-Rainsford, Nathalie

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

43. HIV and Zika virus infection of the male genital tract

Author

Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Dejucq-Rainsford, Nathalie

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

44. Zika virus replicates within the human testis and infects the germ line

Author

Matusali, Giulia, Houzet, Laurent, Satie, Anne-Pascale, Aubry, Florence, Mahé, Dominique, Couderc, Thérèse, Bensalah, Karim, Platel, Christian, Joguet, Guillaume, Bujan, Louis, Cabié, André, Avelar, Gleide, Lecuit, Marc, Le Tortorec, Anna, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], CHU Pointe-à-Pitre/Abymes [Guadeloupe], CHU Toulouse [Toulouse], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Université Paris Descartes - Paris 5 (UPD5), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

45. Zika virus replicates within the human testis and infects the germ line

Author

Matusali, G, Houzet, L, Satie, Anne-Pascale, Mahé, Dominique, Aubry, F., Couderc, T, Frouard, J., Bourgeau, S, Bensalah, K., Platel, C, Joguet, G, Bujan, L, Cabié, A., Avelar, G, Lecuit, Marc, Le Tortorec, Anna, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], coordination hospitalière des prélèvements d'organes et de tissus [CHU Rennes], CHU Pontchaillou [Rennes], Centre Caribéen de Médecine de la Reproduction CECOS CARAIBES (CCMR), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Groupe de recherche en fertilité humaine ( GRFH), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Université Paris Descartes - Paris 5 (UPD5), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), and Institut Pasteur [Paris]

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

46. Seminal SIV in chronically-infected cynomolgus macaques is dominated by virus originating from multiple genital organs

Author

Houzet, Laurent, Pérez-Losada, Marcos, Matusali, Giulia, Deleage, Claire, Dereuddre-Bosquet, Nathalie, Satie, Anne-Pascale, Aubry, Florence, Becker, Emmanuelle, Jégou, Bernard, Le Grand, Roger, Keele, Brandon F, Crandall, Keith A, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), The George Washington University (GW), Universidade do Porto, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Frederick National Laboratory for Cancer Research (FNLCR), National Cancer Institute, National Center for Advancing Translational Sciences, Institut National de la Santé et de la Recherche Médicale, Sidaction, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, District of Columbia Developmental Center for AIDS Research, Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Universidade do Porto = University of Porto

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cynomolgus macaques, Sexual transmission, Phylogenetic analysis, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, viruses, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Simian immunodeficiency virus, HIV, Virus, Single-genome amplification, Male genital organs, Compartmentalization, SIV, Semen, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

International audience; The sexual transmission of viruses is responsible for the spread of multiple infectious diseases. Although the human immunodeficiency virus (HIV)/AIDS pandemic remains fueled by sexual contacts with infected semen, the origin of virus in semen is still unknown. In a substantial number of HIV-infected men, viral strains present in semen differ from the ones in blood, suggesting that HIV is locally produced within the genital tract. Such local production may be responsible for the persistence of HIV in semen despite effective antiretroviral therapy. In this study, we used single-genome amplification, amplicon sequencing ( gene), and phylogenetic analyses to compare the genetic structures of simian immunodeficiency virus (SIV) populations across all the male genital organs and blood in intravenously inoculated cynomolgus macaques in the chronic stage of infection. Examination of the virus populations present in the male genital tissues of the macaques revealed compartmentalized SIV populations in testis, epididymis, vas deferens, seminal vesicles, and urethra. We found genetic similarities between the viral strains present in semen and those in epididymis, vas deferens, and seminal vesicles. The contribution of male genital organs to virus shedding in semen varied among individuals and could not be predicted based on their infection or proinflammatory cytokine mRNA levels. These data indicate that rather than a single source, multiple genital organs are involved in the release of free virus and infected cells into semen. These findings have important implications for our understanding of systemic virus shedding and persistence in semen and for the design of eradication strategies to access viral reservoirs. Semen is instrumental for the dissemination of viruses through sexual contacts. Worryingly, a number of systemic viruses, such as HIV, can persist in this body fluid in the absence of viremia. The local source(s) of virus in semen, however, remains unknown. To elucidate the anatomic origin(s) of the virus released in semen, we compared viral populations present in semen with those in the male genital organs and blood of the Asian macaque model, using single-genome amplification, amplicon sequencing ( gene), and phylogenetic analysis. Our results show that multiple genital tissues harbor compartmentalized strains, some of them (i.e., from epididymis, vas deferens, and seminal vesicles) displaying genetic similarities with the viral populations present in semen. This study is the first to uncover local genital sources of viral populations in semen, providing a new basis for innovative targeted strategies to prevent and eradicate HIV in the male genital tract.

Published
2018

47. In vitro models for deciphering the mechanisms underlying the sexual transmission of viruses at the mucosal level

Author

Frouard, Julie, Le Tortorec, Anna, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genital mucosa, Mucous Membrane, Colon, Rectum, Epithelial Cells, Sexually Transmitted Diseases, Viral, Virus Internalization, Sexually transmitted viruses, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Culture Techniques, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Genitalia, in vitro models
Abstract

International audience; Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.

Published
2018

48. Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI

Author

Hahn Beatrice H, Dejucq-Rainsford Nathalie, Burgener Adam, Forssmann Wolf-Georg, Staendker Ludger, Roan Nadia R, Zirafi Onofrio, Yolamanova Maral, Kim Kyeong-Ae, Shaw George M, Greene Warner C, Kirchhoff Frank, and Münch Jan

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background HIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial. Results Here, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen-mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI. Conclusions Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy.

Published
2010
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49. Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo

Author

Denis Hélène, Satie Anne-Pascale, Le Tortorec Anna, Rioux-Leclercq Nathalie, Havard Laurence, Ruffault Annick, Jégou Bernard, and Dejucq-Rainsford Nathalie

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background In order to determine whether human prostate can be productively infected by HIV-1 strains with different tropism, and thus represent a potential source of HIV in semen, an organotypic culture of prostate from men undergoing prostatic adenomectomy for benign prostate hypertrophy (BPH) was developed. The presence of potential HIV target cells in prostate tissues was investigated using immunohistochemistry. The infection of prostate explants following exposures with HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in culture supernatants, the quantification of HIV DNA in the explants and the detection of HIV RNA+ cells in situ. Results The overall prostate characteristics were retained for 21/2 weeks in culture. Numerous potential HIV-1 target cells were detected in the prostate stroma. Whilst HIV-1 R5SF162 strain consistently productively infected prostatic T lymphocytes and macrophages, the prototypic X4IIIB strain and a primary R5X4 strain showed less efficient replication in this organ. Conclusion The BPH prostate is a site of HIV-1 R5 replication that could contribute virus to semen. A limited spreading of HIV-1 X4 and R5X4 in this organ could participate to the preferential sexual transmission of HIV-1 R5 strains.

Published
2008
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50. Origin of the AIDS virus in semen

Author

Houzet, L, Pérez-Losada, M, Matusali, G, Deleage, C, Dereuddre-Bosquet, N, Satie, A.-P, Jégou, B., Le Grand, R., Keele, B, Crandall, K.A, Dejucq-Rainsford, Nathalie, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), The George Washington University (GW), Basic Research Laboratory [Frederick, MD, USA] (NIH/NCI), Frederick National Laboratory for Cancer Research (FNLCR)-Leidos Biomedical Research, Inc [Frederick, MD, USA], Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Dejucq-Rainsford, Nathalie, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

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