76 results on '"Rosanna Chianese"'
Search Results
2. Antioxidants positively regulate obesity dependent circRNAs - sperm quality - functional axis
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Vincenza Grazia Mele, Teresa Chioccarelli, Rosario Finamore, Antonella D’Agostino, Maria d’Agostino, Donatella Cimini, Monica Mattia, Veronica Porreca, Andrea Maria Giori, Silvia Fasano, Gilda Cobellis, Chiara Schiraldi, Rosanna Chianese, and Francesco Manfrevola
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antioxidant agents ,backsplicing ,circRNAs ,male infertility ,obesity ,oxidative stress ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Obesity is a pathophysiological condition, dependent on body fat accumulation, that progressively induces systemic oxidative stress/inflammation leading to a set of associated clinical manifestations, including male infertility. CircRNAs, covalently closed RNA molecules, are key regulators of sperm quality. Recently, we have characterized a complete profile of high-fat diet (HFD) spermatic circRNA cargo, predicting paternal circRNA dependent networks (ceRNETs), potentially involved in sperm oxidative stress and motility anomalies. In the current work, using HFD C57BL6/J male mice, orally treated with a mix of bioactive molecules (vitamin C; vitamin B12; vitamin E; selenium-L-methionine; glutathione-GSH) for 4 weeks, a reversion of HFD phenotype was observed. In addition, the functional action of the proposed formulations on circRNA biogenesis was evaluated by assessing the endogenous spermatic FUS-dependent backsplicing machinery and related circRNA cargo. After that, spermatic viability and motility were also analyzed. Paternal ceRNETs, potentially involved in oxidative stress regulation and sperm motility defects, were identified and used to suggest that the beneficial action of the food supplements here conveniently formulated on sperm motility was likely due to the recovery of circRNA profile. Such a hypothesis was, then, verified by an in vitro assay.
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- 2023
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3. Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
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Rosalba Senese, Giuseppe Petito, Elena Silvestri, Maria Ventriglia, Nicola Mosca, Nicoletta Potenza, Aniello Russo, Francesco Manfrevola, Gilda Cobellis, Teresa Chioccarelli, Veronica Porreca, Vincenza Grazia Mele, Rosanna Chianese, Pieter de Lange, Giulia Ricci, Federica Cioffi, and Antonia Lanni
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cannabinoid type 1 receptor (CB1) ,skeletal muscle ,mitochondria ,mitochondrial quality control (MQC) ,miRNA ,mitochondrial unfolded protein response (UPRmt) ,Biology (General) ,QH301-705.5 - Abstract
This study aims to explore the complex role of cannabinoid type 1 receptor (CB1) signaling in the gastrocnemius muscle, assessing physiological processes in both CB1+/+ and CB1−/− mice. The primary focus is to enhance our understanding of how CB1 contributes to mitochondrial homeostasis. At the tissue level, CB1−/− mice exhibit a substantial miRNA-related alteration in muscle fiber composition, characterized by an enrichment of oxidative fibers. CB1 absence induces a significant increase in the oxidative capacity of muscle, supported by elevated in-gel activity of Complex I and Complex IV of the mitochondrial respiratory chain. The increased oxidative capacity is associated with elevated oxidative stress and impaired antioxidant defense systems. Analysis of mitochondrial biogenesis markers indicates an enhanced capacity for new mitochondria production in CB1−/− mice, possibly adapting to altered muscle fiber composition. Changes in mitochondrial dynamics, mitophagy response, and unfolded protein response (UPR) pathways reveal a dynamic interplay in response to CB1 absence. The interconnected mitochondrial network, influenced by increased fusion and mitochondrial UPR components, underlines the dual role of CB1 in regulating both protein quality control and the generation of new mitochondria. These findings deepen our comprehension of the CB1 impact on muscle physiology, oxidative stress, and MQC processes, highlighting cellular adaptability to CB1−/−. This study paves the way for further exploration of intricate signaling cascades and cross-talk between cellular compartments in the context of CB1 and mitochondrial homeostasis.
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- 2024
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4. Novel Insights into circRNA Saga Coming from Spermatozoa and Epididymis of HFD Mice
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Francesco Manfrevola, Teresa Chioccarelli, Vincenza Grazia Mele, Veronica Porreca, Monica Mattia, Donatella Cimini, Antonella D’Agostino, Gilda Cobellis, Silvia Fasano, Chiara Schiraldi, Rosanna Chianese, and Riccardo Pierantoni
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circRNAs ,high-fat diet ,spermatozoa ,male infertility ,oxidative stress ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Obesity is a pathophysiological disorder associated with adiposity accumulation, oxidative stress, and chronic inflammation state that is progressively increasing in younger population worldwide, negatively affecting male reproductive skills. An emerging topic in the field of male reproduction is circRNAs, covalently closed RNA molecules produced by backsplicing, actively involved in a successful spermatogenesis and in establishing high-quality sperm parameters. However, a direct correlation between obesity and impaired circRNA cargo in spermatozoa (SPZ) remains unclear. In the current work, using C57BL6/J male mice fed with a high-fat diet (HFD, 60% fat) as experimental model of oxidative stress, we investigated the impact of HFD on sperm morphology and motility as well as on spermatic circRNAs. We performed a complete dataset of spermatic circRNA content by a microarray strategy, and differentially expressed (DE)-circRNAs were identified. Using a circRNA/miRNA/target network (ceRNET) analysis, we identified circRNAs potentially involved in oxidative stress and sperm motility pathways. Interestingly, we demonstrated an enhanced skill of HFD sperm in backsplicing activity together with an inefficient epididymal circRNA biogenesis. Fused protein in sarcoma (FUS) and its ability to recruit quaking (QKI) could be involved in orchestrating such mechanism.
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- 2023
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5. KISS1R and ANKRD31 Cooperate to Enhance Leydig Cell Gene Expression via the Cytoskeletal-Nucleoskeletal Pathway
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Giulia Ricci, Florian Guillou, Angela Catizone, Vincenza Grazia Mele, Martina Moggio, Teresa Chioccarelli, Nadia Diano, Rosaria Meccariello, Riccardo Pierantoni, Silvia Fasano, Gilda Cobellis, Rosanna Chianese, and Francesco Manfrevola
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kisspeptin ,KISS1R ,ankyrins ,male fertility ,Leydig cells ,cytoskeletal–nucleoskeletal pathway ,Biology (General) ,QH301-705.5 - Abstract
Kisspeptins are involved in the regulation of hypothalamic-pituitary-gonadal axis, Leydig cell functions, and testosterone secretion, acting as endogenous ligands of the KISS1 receptor. ANKRD31 protein participates in male fertility, regulating meiotic progression, and epididymal sperm maturation. Here, we show that in Leydig cells, KISS1 receptor and ANKRD31 proteins physically interact; the formation of this protein complex is enhanced by Kisspeptin-10 that also modulates F-actin synthesis, favoring histone acetylation in chromatin and gene expression via the cytoskeletal–nucleoskeletal pathway. Kp/KISS1R system deregulation, expression impairment of cytoskeletal–nucleoskeletal mediators, Leydig gene targets, and the decreased testosterone secretion in Ankrd31−/− testis strongly supported our hypothesis. Furthermore, cytochalasin D treatment subverted the gene expression induction dependent on Kisspeptin-10 action. In conclusion, the current work highlights a novel role for the Kisspeptin-10 in the induction of the cytoskeletal–nucleoskeletal route, downstream a physical interaction between KISS1 receptor and ANKRD31, with gene expression activation as final effect, in Leydig cells.
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- 2022
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6. Ankrd31 in Sperm and Epididymal Integrity
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Francesco Manfrevola, Guillaume Martinez, Charles Coutton, Domenico Rocco, Karine Reynaud, Yves Le Vern, Pascal Froment, Linda Beauclair, Denise Aubert, Riccardo Pierantoni, Rosanna Chianese, and Florian Guillou
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ankyrins ,spermatogenesis ,sperm quality ,blood-epididymal-barrier ,male infertility ,Biology (General) ,QH301-705.5 - Abstract
Ankyrin proteins (ANKRD) are key mediators linking membrane and sub-membranous cytoskeletal proteins. Recent findings have highlighted a new role of ANKRD31 during spermatogenesis, elucidating its involvement in meiotic recombination and male germ cell progression. Following testicular differentiation, spermatozoa (SPZ) enter into the epididymis, where they undergo several biochemical and enzymatic changes. The epididymal epithelium is characterized by cell-to-cell junctions that are able to form the blood-epididymal barrier (BEB). This intricate epithelial structure provides the optimal microenvironment needed for epididymal sperm maturation. To date, no notions have been reported regarding a putative role of ANKRD31 in correct BEB formation. In our work, we generated an Ankrd31 knockout male mouse model (Ankrd31–/–) and characterized its reproductive phenotype. Ankrd31–/– mice were infertile and exhibited oligo-astheno-teratozoospermia (a low number of immotile SPZ with abnormal morphological features). In addition, a complete deregulation of BEB was found in Ankrd31–/–, due to cell-to-cell junction anomalies. In order to suggest that BEB deregulation may depend on Ankrd31 gene deletion, we showed the physical interaction among ANKRD31 and some epithelial junction proteins in wild-type (WT) epididymides. In conclusion, the current work shows a key role of ANKRD31 in the control of germ cell progression as well as sperm and epididymal integrity.
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- 2021
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7. CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia
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Francesco Manfrevola, Teresa Chioccarelli, Gilda Cobellis, Silvia Fasano, Bruno Ferraro, Carolina Sellitto, Giovanni Marella, Riccardo Pierantoni, and Rosanna Chianese
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circRNAs ,epigenetic signature ,infertility ,asthenozoospermia ,mitochondria-dependent ceRNET ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
The role of circRNA in reproduction is under investigation. CircRNAs are expressed in human testis, spermatozoa (SPZ), and seminal plasma. Their involvement in embryo development has also been suggested. Asthenozoospermia, a common cause of male infertility, is characterized by reduced or absent sperm motility in fresh ejaculate. While abnormal mitochondrial function, altered sperm tail, and genomic causes have been deeply investigated, the epigenetic signature of asthenozoospermic derived SPZ still remains unexplored. CircRNAs may take part in the repertoire of differentially expressed molecules in infertile men. Considering this background, we carried out a circRNA microarray, identifying a total of 9,138 transcripts, 22% of them novel based and 83.5% with an exonic structure. Using KEGG analysis, we evaluated the circRNA contribution in pathways related to mitochondrial function and sperm motility. In order to discriminate circRNAs with a differential expression in SPZ with differential morphological parameters, we separated sperm cells by Percoll gradient and analyzed their differential circRNA payload. A bioinformatic approach was then utilized to build a circRNA/miRNA/mRNA network. With the aim to demonstrate a dynamic contribution of circRNAs to the sperm epigenetic signature, we verified their modulation as a consequence of an oral amino acid supplementation, efficacious in improving SPZ motility.
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- 2020
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8. CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen
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Francesco Manfrevola, Bruno Ferraro, Carolina Sellitto, Domenico Rocco, Silvia Fasano, Riccardo Pierantoni, and Rosanna Chianese
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circRNAs ,mRNAs ,sperm motility ,asthenozoospermia ,sperm quality ,Cytology ,QH573-671 - Abstract
The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular RNAs (circRNAs) are involved in microRNA (miRNA) inhibition by a sponge activity to protect mRNA targets. All together they form the competitive endogenous RNA network (ceRNET). Recently, we have identified differentially expressed circRNAs (DE-circRNAs) in normozoospermic and asthenozoospermic patients, associated with high-quality (A-spermatozoa) and low-quality (B-spermatozoa) sperm. Here, we carried out a differential analysis of CRISP2, CATSPER1 and PATE1 mRNA expression in good quality (A-spermatozoa) and low quality (B-spermatozoa) sperm fractions collected from both normozoospermic volunteers and asthenozoospermic patients. These sperm fractions are usually separated on the basis of morphology and motility parameters by a density gradient centrifugation. B-spermatozoa showed low levels of mRNAs. Thus, we identified the possible ceRNET responsible for regulating their expression by focusing on circTRIM2, circEPS15 and circRERE. With the idea that motility perturbations could be rooted in quantitative changes of transcripts in sperm, we evaluated circRNA and mRNA modulation in A-spermatozoa and B-spermatozoa after an oral amino acid supplementation known to improve sperm motility. The profiles of CRISP2, CATSPER1 and PATE1 proteins in the same fractions of sperm well matched with the transcript levels. Our data may strengthen the role of circRNAs in asthenozoospermia and shed light on the molecular pathways linked to sperm motility regulation.
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- 2021
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9. LINCking the Nuclear Envelope to Sperm Architecture
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Francesco Manfrevola, Florian Guillou, Silvia Fasano, Riccardo Pierantoni, and Rosanna Chianese
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LINC complex ,SUN ,KASH ,actin ,spermatozoa ,male fertility ,Genetics ,QH426-470 - Abstract
Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility.
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- 2021
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10. Expression Patterns of Circular RNAs in High Quality and Poor Quality Human Spermatozoa
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Teresa Chioccarelli, Francesco Manfrevola, Bruno Ferraro, Carolina Sellitto, Gilda Cobellis, Marina Migliaccio, Silvia Fasano, Riccardo Pierantoni, and Rosanna Chianese
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circRNAs ,spermatozoa ,miRNAs ,sperm quality ,fertilization ,embryo development ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Circular RNAs (circRNAs) are expressed in human testis and seminal plasma. Until today, there is missing information about a possible payload of circRNAs in human spermatozoa (SPZ). With this in mind, we carried out a circRNA microarray identifying a total of 10.726 transcripts, 28% novel based and 84.6% with exonic structure; their potential contribution in molecular pathways was evaluated by KEGG analysis. Whether circRNAs may be related to SPZ quality was speculated evaluating two different populations of SPZ (A SPZ = good quality, B SPZ = low quality), separated on the basis of morphology and motility parameters, by Percoll gradient. Thus, 148 differentially expressed (DE)-circRNAs were identified and the expression of selected specific SPZ-derived circRNAs was evaluated in SPZ head/tail-enriched preparations, to check the preservation of these molecules during SPZ maturation and their transfer into oocyte during fertilization. Lastly, circRNA/miRNA/mRNA network was built by bioinformatics approach.
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- 2019
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11. Editorial: The Multiple Facets of Kisspeptin Activity in Biological Systems
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Rosanna Chianese, William H. Colledge, Silvia Fasano, and Rosaria Meccariello
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Kisspeptin ,cancer ,reproduction ,puberty ,metabolism ,comparative genomics ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Published
- 2018
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12. Mitochondrial Reactive Oxygen Species (ROS) Production Alters Sperm Quality
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Rosanna Chianese and Riccardo Pierantoni
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oxidative stress ,sperm physiology ,ROS impact on sperm quality ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic pathway, and the generation of reactive oxygen species (ROS). Despite the loss of the majority of the cytoplasm occurring during spermiogenesis, mammalian sperm preserves a number of mitochondria that rearrange in a tubular structure at the level of the sperm flagellum midpiece. Although sperm mitochondria are destroyed inside the zygote, the integrity and the functionality of these organelles seem to be critical for fertilization and embryo development. The aim of this review was to discuss the impact of mitochondria-produced ROS at multiple levels in sperm: the genome, proteome, lipidome, epigenome. How diet, aging and environmental pollution may affect sperm quality and offspring health—by exacerbating oxidative stress—will be also described.
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- 2021
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13. Exosome Composition and Seminal Plasma Proteome: A Promising Source of Biomarkers of Male Infertility
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Luz Candenas and Rosanna Chianese
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sperm ,seminal plasma ,seminal exosomes ,infertility ,seminal proteins ,biomarkers ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Infertility has become a global health issue, with approximately 50% of infertility cases generated by disorders in male reproduction. Spermatozoa are conveyed towards female genital tracts in a safe surrounding provided by the seminal plasma. Interestingly, this dynamically changing medium is a rich source of proteins, essential not only for sperm transport, but also for its protection and maturation. Most of the seminal proteins are acquired by spermatozoa in transit through exosomes (epididymosomes and prostasomes). The high number of seminal proteins, the increasing knowledge of their origins and biological functions and their differential expression in the case of azoospermia, asthenozoospermia, oligozoospermia and teratozoospermia or other conditions of male infertility have allowed the identification of a wide variety of biomarker candidates and their involvement in biological pathways, thus to strongly suggest that the proteomic landscape of seminal plasma may be a potential indicator of sperm dysfunction. This review summarizes the current knowledge in seminal plasma proteomics and its potentiality as a diagnostic tool in different degrees of male infertility.
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- 2020
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14. Environmental Impact on Male (In)Fertility via Epigenetic Route
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Matilde Cescon, Rosanna Chianese, and Renata S. Tavares
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epigenetic signature of germ cells ,sperm epigenome ,environmental pollutant ,diet impact on epigenetic route ,Medicine - Abstract
In the last 40 years, male reproductive health—which is very sensitive to both environmental exposure and metabolic status—has deteriorated and the poor sperm quality observed has been suggested to affect offspring development and its health in adult life. In this scenario, evidence now suggests that epigenetics shapes endocrine functions, linking genetics and environment. During fertilization, spermatozoa share with the oocyte their epigenome, along with their haploid genome, in order to orchestrate embryo development. The epigenetic signature of spermatozoa is the result of a dynamic modulation of the epigenetic marks occurring, firstly, in the testis—during germ cell progression—then, along the epididymis, where spermatozoa still receive molecules, conveyed by epididymosomes. Paternal lifestyle, including nutrition and exposure to hazardous substances, alters the phenotype of the next generations, through the remodeling of a sperm epigenetic blueprint that dynamically reacts to a wide range of environmental and lifestyle stressors. With that in mind, this review will summarize and discuss insights into germline epigenetic plasticity caused by environmental stimuli and diet and how spermatozoa may be carriers of induced epimutations across generations through a mechanism known as paternal transgenerational epigenetic inheritance.
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- 2020
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15. Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality
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Teresa Chioccarelli, Riccardo Pierantoni, Francesco Manfrevola, Veronica Porreca, Silvia Fasano, Rosanna Chianese, and Gilda Cobellis
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histone post-translational modifications (histone ptms) ,circular rnas (circrnas) ,human male infertility ,sperm ,spermatogenesis ,fertilization ,embryo development ,Medicine - Abstract
Spermatozoa (SPZ) are motile cells, characterized by a cargo of epigenetic information including histone post-translational modifications (histone PTMs) and non-coding RNAs. Specific histone PTMs are present in developing germ cells, with a key role in spermatogenic events such as self-renewal and commitment of spermatogonia (SPG), meiotic recombination, nuclear condensation in spermatids (SPT). Nuclear condensation is related to chromatin remodeling events and requires a massive histone-to-protamine exchange. After this event a small percentage of chromatin is condensed by histones and SPZ contain nucleoprotamines and a small fraction of nucleohistone chromatin carrying a landascape of histone PTMs. Circular RNAs (circRNAs), a new class of non-coding RNAs, characterized by a nonlinear back-spliced junction, able to play as microRNA (miRNA) sponges, protein scaffolds and translation templates, have been recently characterized in both human and mouse SPZ. Since their abundance in eukaryote tissues, it is challenging to deepen their biological function, especially in the field of reproduction. Here we review the critical role of histone PTMs in male germ cells and the profile of circRNAs in mouse and human SPZ. Furthermore, we discuss their suggested role as novel epigenetic biomarkers to assess sperm quality and improve artificial insemination procedure.
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- 2020
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16. Cannabinoids and Reproduction: A Lasting and Intriguing History
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Gilda Cobellis, Silvia Fasano, Riccardo Pierantoni, Vincenza Ciaramella, Teresa Chioccarelli, Giovanna Cacciola, Rosanna Chianese, and Rosaria Meccariello
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cannabinergic system, male reproduction, female reproduction, hypothalamus-pituitary-gonads axis. ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Starting from an historical overview of lasting Cannabis use over the centuries, we will focus on a description of the cannabinergic system, with a comprehensive analysis of chemical and pharmacological properties of endogenous and synthetic cannabimimetic analogues. The metabolic pathways and the signal transduction mechanisms, activated by cannabinoid receptors stimulation, will also be discussed. In particular, we will point out the action of cannabinoids and endocannabinoids on the different neuronal networks involved in reproductive axis, and locally, on male and female reproductive tracts, by emphasizing the pivotal role played by this system in the control of fertility.
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- 2010
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17. Expression Analysis of Gnrh1 and Gnrhr1 in Spermatogenic Cells of Rat
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Vincenza Ciaramella, Rosanna Chianese, Paolo Pariante, Silvia Fasano, Riccardo Pierantoni, and Rosaria Meccariello
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Hypothalamic Gonadotropin Releasing Hormone (GnRH), via GnRH receptor (GnRHR), is the main actor in the control of reproduction, in that it induces the biosynthesis and the release of pituitary gonadotropins, which in turn promote steroidogenesis and gametogenesis in both sexes. Extrabrain functions of GnRH have been extensively described in the past decades and, in males, local GnRH activity promotes the progression of spermatogenesis and sperm functions at several levels. The canonical localization of Gnrh1 and Gnrhr1 mRNA is Sertoli and Leydig cells, respectively, but ligand and receptor are also expressed in germ cells. Here, we analysed the expression rate of Gnrh1 and Gnrhr1 in rat testis (180 days old) by quantitative real-time PCR (qPCR) and by in situ hybridization we localized Gnrh1 and Gnrhr1 mRNA in different spermatogenic cells of adult animals. Our data confirm the testicular expression of Gnrh1 and of Gnrhr1 in somatic cells and provide evidence that their expression in the germinal compartment is restricted to haploid cells. In addition, not only Sertoli cells connected to spermatids in the last steps of maturation but also Leydig and peritubular myoid cells express Gnrh1.
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- 2015
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18. Endocannabinoids and Endovanilloids: A Possible Balance in the Regulation of the Testicular GnRH Signalling
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Rosanna Chianese, Vincenza Ciaramella, Donatella Scarpa, Silvia Fasano, Riccardo Pierantoni, and Rosaria Meccariello
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Reproductive functions are regulated both at central (brain) and gonadal levels. In this respect, the endocannabinoid system (eCS) has a very influential role. Interestingly, the characterization of eCS has taken many advantages from the usage of animal models different from mammals. Therefore, this review is oriented to summarize the main pieces of evidence regarding eCS coming from the anuran amphibian Rana esculenta, with particular interest to the morphofunctional relationship between eCS and gonadotropin releasing hormone (GnRH). Furthermore, a novel role for endovanilloids in the regulation of a testicular GnRH system will be also discussed.
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- 2013
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19. Spermatozoa: Facts and Perspectives
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Rosaria Meccariello, Rosanna Chianese and Rosaria Meccariello, Rosanna Chianese
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- 2018
20. Cannabinoids in Health and Disease
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Rosaria Meccariello, Rosanna Chianese and Rosaria Meccariello, Rosanna Chianese
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- 2016
21. Actin remodeling driven by circLIMA1: sperm cell as an intriguing cellular model
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Francesco Manfrevola, Nicoletta Potenza, Teresa Chioccarelli, Armando Di Palo, Chiara Siniscalchi, Veronica Porreca, Arcangelo Scialla, Vincenza Grazia Mele, Giuseppe Petito, Aniello Russo, Antonia Lanni, Rosalba Senese, Giulia Ricci, Riccardo Pierantoni, Rosanna Chianese, Gilda Cobellis, Manfrevola, Francesco, Potenza, Nicoletta, Chioccarelli, Teresa, DI PALO, Armando, Siniscalchi, Chiara, Porreca, Veronica, Scialla, Arcangelo, Grazia Mele, Vincenza, Petito, Giuseppe, Russo, Aniello, Lanni, Antonia, Senese, Rosalba, Ricci, Giulia, Pierantoni, Riccardo, Chianese, Rosanna, and Cobellis, Gilda
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Male ,spermatozoa ,QKI ,RNA, Circular ,Cell Biology ,Spermatozoa ,Applied Microbiology and Biotechnology ,CB1 ,Actins ,Mice ,Semen ,Animals ,circRNA ,Molecular Biology ,actin ,Ecology, Evolution, Behavior and Systematics ,Gelsolin ,Endocannabinoids ,Developmental Biology - Abstract
CircRNA cargo in spermatozoa (SPZ) participates in setting cell quality, in terms of morphology and motility. Cannabinoid receptor CB1 activity is correlated with a proper spermatogenesis and epididymal sperm maturation. Despite CB1 promotes endogenous skill to circularize mRNAs in SPZ, few notions are reported regarding the functional link between endocannabinoids and spermatic circRNA cargo. In CB1 knock-out male mice, we performed a complete dataset of spermatic circRNA content by microarray strategy. Differentially expressed (DE)-circRNAs, as a function of genotype, were identified. Within DE-circRNAs, we focused the attention on circLIMA1, as putative actin-cytoskeleton architecture regulator. The validation of circLIMA1 dependent-competitive endogenous RNA (ceRNA) network (ceRNET) in in vitro cell line confirmed its activity in the regulation of the cytoskeletal actin. Interestingly, a dynamic actin regulation in SPZ nuclei was found during their epididymal maturation. In this scenario, we showed for the first time an intriguing sperm nuclear actin remodeling, regulated via a ceRNET-independent pathway, consisting in the nuclear shuttling of circLIMA1-QKI interactome and downstream in Gelsolin regulation. In particular, the increased levels of circLIMA1 in CB1 knock-out SPZ, associated with an inefficient depolymerization of nuclear actin, specifically illustrate how endocannabinoids, by regulating circRNA cargo, may contribute to sperm morpho-cellular maturation.
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- 2022
22. Neuro-toxic and Reproductive Effects of BPA
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Rosaria Meccariello, Stefania Lucia Nori, Sean Richards, Silvia Fasano, Rosanna Chianese, Jacopo Troisi, Andrea Viggiano, Maurizio Guida, Antonietta Santoro, Elizabeth Plunk, Riccardo Pierantoni, Santoro, A, Chianese, R, Troisi, J, Richards, S, Nori, Sl, Fasano, S, Guida, M, Plunk, E, Viggiano, A, Pierantoni, R, Meccariello, R, Santoro, Antonietta, Chianese, Rosanna, Troisi, Jacopo, Richards, Sean, Nori, Stefania Lucia, Fasano, Silvia, Guida, Maurizio, Plunck, Elizabeth, Viggiano, Andrea, Pierantoni, Riccardo, and Meccariello, Rosaria
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0301 basic medicine ,endocrine system ,BPA, neuronal differentiation, synaptic plasticity, neuroinflammation, epigenetics, hypothalamus, HPG axis, GnRH, Kiss1, reproduction ,HPG axi ,Hypothalamic–pituitary–gonadal axis ,Gonadotropin-releasing hormone ,Biology ,Article ,neuroinflammation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Phenols ,medicine ,Premovement neuronal activity ,Animals ,Humans ,Pharmacology (medical) ,hypothalamus ,Benzhydryl Compounds ,neuronal differentiation ,Neuroinflammation ,Pharmacology ,Neurons ,synaptic plasticity ,epigenetics ,urogenital system ,Reproduction ,Neurotoxicity ,General Medicine ,Kiss1 ,medicine.disease ,hypothalamu ,BPA ,Psychiatry and Mental health ,030104 developmental biology ,Neurology ,chemistry ,Hypothalamus ,GnRH ,Synaptic plasticity ,Neurology (clinical) ,HPG axis ,Neuroscience ,epigenetic ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,Toxicant - Abstract
Background:Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine-disrupting chemical and has suspected roles as a neurological and reproductive toxicant. It interferes in steroid signaling, induces oxidative stress, and affects gene expression epigenetically. Gestational, perinatal and neonatal exposures to BPA affect developmental processes, including brain development and gametogenesis, with consequences on brain functions, behavior, and fertility.Methods:This review critically analyzes recent findings on the neuro-toxic and reproductive effects of BPA (and its analogues), with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction.Results:BPA has potential human health hazard associated with gestational, peri- and neonatal exposure. Beginning with BPA’s disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal differentiation, synaptic plasticity, neuroinflammation, neuro-degeneration, and impairment of cognitive abilities. Furthermore, it reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releasing Hormone (GnRH), and the associated effects on reproduction in both sexes and successful pregnancy.Conclusion:BPA and its analogues impair neuronal activity, HPG axis function, reproduction, and fertility. Contrasting results have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This review offers new insights on these issues with the aim to find the “fil rouge”, if any, that characterize BPA’s mechanism of action with outcomes on neuronal function and reproduction.
- Published
- 2019
23. FUS driven circCNOT6L biogenesis in mouse and human spermatozoa supports zygote development
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Teresa Chioccarelli, Geppino Falco, Donato Cappetta, Antonella De Angelis, Luca Roberto, Martina Addeo, Marco Ragusa, Davide Barbagallo, Liberato Berrino, Michele Purrello, Concetta Ambrosino, Gilda Cobellis, Riccardo Pierantoni, Rosanna Chianese, Francesco Manfrevola, Chioccarelli, T., Falco, G., Cappetta, D., De Angelis, A., Roberto, L., Addeo, M., Ragusa, M., Barbagallo, D., Berrino, L., Purrello, M., Ambrosino, C., Cobellis, G., Pierantoni, R., Chianese, R., and Manfrevola, F.
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Male ,Zygote ,Knockout ,Circular ,Embryo development ,Mice ,Cellular and Molecular Neuroscience ,Ribonucleases ,Animals ,Humans ,circRNA ,Molecular Biology ,Mice, Knockout ,Pharmacology ,Cannabinoid receptor I ,Backsplicing ,Sperm maturation ,RNA, Circular ,Cell Biology ,Spermatozoa ,Oocytes ,RNA ,RNA-Binding Protein FUS ,Molecular Medicine ,Female ,Original Article ,circRNAs - Abstract
Circular RNA (circRNA) biogenesis requires a backsplicing reaction, promoted by inverted repeats in cis-flanking sequences and trans factors, such as RNA-binding proteins (RBPs). Among these, FUS plays a key role. During spermatogenesis and sperm maturation along the epididymis such a molecular mechanism has been poorly explored. With this in mind, we chose circCNOT6L as a study case and wild-type (WT) as well as cannabinoid receptor type-1 knock-out (Cb1−/−) male mice as animal models to analyze backsplicing mechanisms. Our results suggest that spermatozoa (SPZ) have an endogenous skill to circularize mRNAs, choosing FUS as modulator of backsplicing and under CB1 stimulation. A physical interaction between FUS and CNOT6L as well as a cooperation among FUS, RNA Polymerase II (RNApol2) and Quaking (QKI) take place in SPZ. Finally, to gain insight into FUS involvement in circCNOT6L biogenesis, FUS expression was reduced through RNA interference approach. Paternal transmission of FUS and CNOT6L to oocytes during fertilization was then assessed by using murine unfertilized oocytes (NF), one-cell zygotes (F) and murine oocytes undergoing parthenogenetic activation (PA) to exclude a maternal contribution. The role of circCNOT6L as an active regulator of zygote transition toward the 2-cell-like state was suggested using the Embryonic Stem Cell (ESC) system. Intriguingly, human SPZ exactly mirror murine SPZ.
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- 2021
24. LINCking the Nuclear Envelope to Sperm Architecture
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Florian Guillou, Riccardo Pierantoni, Rosanna Chianese, Francesco Manfrevola, Silvia Fasano, Università degli studi della Campania 'Luigi Vanvitelli', Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Manfrevola, F, Guillou, F, Fasano, Silvia, Pierantoni, R, Chianese, R, and Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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0301 basic medicine ,Male ,KASH ,Spermiogenesis ,Nuclear Envelope ,[SDV]Life Sciences [q-bio] ,LINC complex ,Review ,QH426-470 ,Biology ,Flagellum ,Mechanotransduction, Cellular ,male fertility ,03 medical and health sciences ,0302 clinical medicine ,Spermatocytes ,Genetics ,medicine ,Animals ,Humans ,Nuclear Matrix ,Nuclear membrane ,Cytoskeleton ,Integral membrane protein ,Genetics (clinical) ,Infertility, Male ,Cell Nucleus ,SUN ,Subcellular localization ,Sperm ,Spermatids ,Spermatozoa ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,actin - Abstract
International audience; Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility.
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- 2021
25. Mitochondrial Reactive Oxygen Species (ROS) Production Alters Sperm Quality
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Riccardo Pierantoni, Rosanna Chianese, Chianese, R, and Pierantoni, R
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0301 basic medicine ,Physiology ,Clinical Biochemistry ,Environmental pollution ,Oxidative phosphorylation ,Review ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,oxidative stress ,Molecular Biology ,chemistry.chemical_classification ,sperm physiology ,Reactive oxygen species ,030219 obstetrics & reproductive medicine ,Zygote ,Sperm flagellum ,urogenital system ,lcsh:RM1-950 ,ROS impact on sperm quality ,Cell Biology ,Sperm ,Cell biology ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,chemistry ,Oxidative stress - Abstract
Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic pathway, and the generation of reactive oxygen species (ROS). Despite the loss of the majority of the cytoplasm occurring during spermiogenesis, mammalian sperm preserves a number of mitochondria that rearrange in a tubular structure at the level of the sperm flagellum midpiece. Although sperm mitochondria are destroyed inside the zygote, the integrity and the functionality of these organelles seem to be critical for fertilization and embryo development. The aim of this review was to discuss the impact of mitochondria-produced ROS at multiple levels in sperm: the genome, proteome, lipidome, epigenome. How diet, aging and environmental pollution may affect sperm quality and offspring health—by exacerbating oxidative stress—will be also described.
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- 2021
26. Ankrd31 nécessaire à l'intégrité du sperme et de l'épididyme
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Yves Le Vern, Denise Aubert, Karine Reynaud, Florian Guillou, Pascal Froment, Riccardo Pierantoni, Guillaume Martinez, Francesco Manfrevola, Linda Beauclair, Rosanna Chianese, Charles Coutton, Domenico Rocco, Manfrevola, F, Martinez, G, Coutton, C, Rocco, D, Reynaud, K, Le Vern, Y, Froment, P, Beauclair, L, Aubert, D, Pierantoni, R, Chianese, R, Guillou, F, Università degli studi della Campania 'Luigi Vanvitelli', Centre Hospitalier Universitaire [Grenoble] (CHU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Froment, Pascal, Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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sperm quality ,QH301-705.5 ,ankyrins ,[SDV]Life Sciences [q-bio] ,Biology ,male infertility ,Male infertility ,[SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction ,03 medical and health sciences ,Cell and Developmental Biology ,0302 clinical medicine ,blood-epididymal-barrier ,medicine ,Ankyrin ,Biology (General) ,030304 developmental biology ,Original Research ,chemistry.chemical_classification ,0303 health sciences ,030219 obstetrics & reproductive medicine ,Cell Biology ,medicine.disease ,Epididymis ,Sperm ,Phenotype ,spermatogenesis ,Cell biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,chemistry ,Homologous recombination ,Spermatogenesis ,Germ cell ,Developmental Biology - Abstract
Ankyrin proteins (ANKRD) are key mediators linking membrane and sub-membranous cytoskeletal proteins. Recent findings have highlighted a new role of ANKRD31 during spermatogenesis, elucidating its involvement in meiotic recombination and male germ cell progression. Following testicular differentiation, spermatozoa (SPZ) enter into the epididymis, where they undergo several biochemical and enzymatic changes. The epididymal epithelium is characterized by cell-to-cell junctions that are able to form the blood-epididymal barrier (BEB). This intricate epithelial structure provides the optimal microenvironment needed for epididymal sperm maturation. To date, no notions have been reported regarding a putative role of ANKRD31 in correct BEB formation. In our work, we generated an Ankrd31 knockout male mouse model (Ankrd31–/–) and characterized its reproductive phenotype. Ankrd31–/– mice were infertile and exhibited oligo-astheno-teratozoospermia (a low number of immotile SPZ with abnormal morphological features). In addition, a complete deregulation of BEB was found in Ankrd31–/–, due to cell-to-cell junction anomalies. In order to suggest that BEB deregulation may depend on Ankrd31 gene deletion, we showed the physical interaction among ANKRD31 and some epithelial junction proteins in wild-type (WT) epididymides. In conclusion, the current work shows a key role of ANKRD31 in the control of germ cell progression as well as sperm and epididymal integrity.
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- 2021
27. CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen
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Bruno Ferraro, Carolina Sellitto, Silvia Fasano, Riccardo Pierantoni, Rosanna Chianese, Domenico Rocco, Francesco Manfrevola, Manfrevola, F, Ferraro, B, Sellitto, Carolina, Rocco, D, Fasano, Silvia, Pierantoni, R, and Chianese, R
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0301 basic medicine ,endocrine system ,sperm quality ,QH301-705.5 ,mRNAs ,Motility ,Semen ,Biology ,Asthenozoospermia ,Article ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,sperm motility ,Biology (General) ,Sperm motility ,reproductive and urinary physiology ,asthenozoospermia ,Messenger RNA ,030219 obstetrics & reproductive medicine ,urogenital system ,RNA ,General Medicine ,medicine.disease ,Sperm ,Cell biology ,030104 developmental biology ,circRNAs - Abstract
The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular RNAs (circRNAs) are involved in microRNA (miRNA) inhibition by a sponge activity to protect mRNA targets. All together they form the competitive endogenous RNA network (ceRNET). Recently, we have identified differentially expressed circRNAs (DE-circRNAs) in normozoospermic and asthenozoospermic patients, associated with high-quality (A-spermatozoa) and low-quality (B-spermatozoa) sperm. Here, we carried out a differential analysis of CRISP2, CATSPER1 and PATE1 mRNA expression in good quality (A-spermatozoa) and low quality (B-spermatozoa) sperm fractions collected from both normozoospermic volunteers and asthenozoospermic patients. These sperm fractions are usually separated on the basis of morphology and motility parameters by a density gradient centrifugation. B-spermatozoa showed low levels of mRNAs. Thus, we identified the possible ceRNET responsible for regulating their expression by focusing on circTRIM2, circEPS15 and circRERE. With the idea that motility perturbations could be rooted in quantitative changes of transcripts in sperm, we evaluated circRNA and mRNA modulation in A-spermatozoa and B-spermatozoa after an oral amino acid supplementation known to improve sperm motility. The profiles of CRISP2, CATSPER1 and PATE1 proteins in the same fractions of sperm well matched with the transcript levels. Our data may strengthen the role of circRNAs in asthenozoospermia and shed light on the molecular pathways linked to sperm motility regulation.
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- 2021
28. Environmental Impact on Male (In)Fertility via Epigenetic Route
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Rosanna Chianese, Matilde Cescon, Renata S. Tavares, Cescon, Matilde, Chianese, Rosanna, and S Tavares, Renata
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endocrine system ,Offspring ,lcsh:Medicine ,Review ,epigenetic signature of germ cells ,Germline ,03 medical and health sciences ,0302 clinical medicine ,medicine ,diet impact on epigenetic route ,environmental pollutant ,sperm epigenome ,Epigenetics ,030304 developmental biology ,Genetics ,0303 health sciences ,030219 obstetrics & reproductive medicine ,business.industry ,Mechanism (biology) ,lcsh:R ,General Medicine ,Epigenome ,Environmental exposure ,Sperm ,medicine.anatomical_structure ,business ,Germ cell - Abstract
In the last 40 years, male reproductive health—which is very sensitive to both environmental exposure and metabolic status—has deteriorated and the poor sperm quality observed has been suggested to affect offspring development and its health in adult life. In this scenario, evidence now suggests that epigenetics shapes endocrine functions, linking genetics and environment. During fertilization, spermatozoa share with the oocyte their epigenome, along with their haploid genome, in order to orchestrate embryo development. The epigenetic signature of spermatozoa is the result of a dynamic modulation of the epigenetic marks occurring, firstly, in the testis—during germ cell progression—then, along the epididymis, where spermatozoa still receive molecules, conveyed by epididymosomes. Paternal lifestyle, including nutrition and exposure to hazardous substances, alters the phenotype of the next generations, through the remodeling of a sperm epigenetic blueprint that dynamically reacts to a wide range of environmental and lifestyle stressors. With that in mind, this review will summarize and discuss insights into germline epigenetic plasticity caused by environmental stimuli and diet and how spermatozoa may be carriers of induced epimutations across generations through a mechanism known as paternal transgenerational epigenetic inheritance.
- Published
- 2020
29. CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia
- Author
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Riccardo Pierantoni, Rosanna Chianese, Bruno Ferraro, Francesco Manfrevola, Teresa Chioccarelli, Gilda Cobellis, Giovanni Marella, Carolina Sellitto, Silvia Fasano, Manfrevola, Francesco, Chioccarelli, Teresa, Cobellis, Gilda, Fasano, Silvia, Ferraro, Bruno, Sellitto, Carolina, Marella, Giovanni, Pierantoni, Riccardo, and Chianese, Rosanna
- Subjects
0301 basic medicine ,Adult ,Male ,Microarray ,Endocrinology, Diabetes and Metabolism ,epigenetic signature ,Gene Expression ,030209 endocrinology & metabolism ,Biology ,Asthenozoospermia ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,mitochondria-dependent ceRNET ,Male infertility ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,microRNA ,medicine ,Humans ,Epigenetics ,KEGG ,Sperm motility ,Original Research ,lcsh:RC648-665 ,Computational Biology ,RNA, Circular ,medicine.disease ,Microarray Analysis ,Sperm ,Spermatozoa ,Cell biology ,030104 developmental biology ,Sperm Motility ,asthenozoospermia, circRNAs, epigenetic signature, infertility, mitochondria-dependent ceRNET ,circRNAs ,infertility - Abstract
The role of circRNA in reproduction is under investigation. CircRNAs are expressed in human testis, spermatozoa (SPZ), and seminal plasma. Their involvement in embryo development has also been suggested. Asthenozoospermia, a common cause of male infertility, is characterized by reduced or absent sperm motility in fresh ejaculate. While abnormal mitochondrial function, altered sperm tail, and genomic causes have been deeply investigated, the epigenetic signature of asthenozoospermic derived SPZ still remains unexplored. CircRNAs may take part in the repertoire of differentially expressed molecules in infertile men. Considering this background, we carried out a circRNA microarray, identifying a total of 9,138 transcripts, 22% of them novel based and 83.5% with an exonic structure. Using KEGG analysis, we evaluated the circRNA contribution in pathways related to mitochondrial function and sperm motility. In order to discriminate circRNAs with a differential expression in SPZ with differential morphological parameters, we separated sperm cells by Percoll gradient and analyzed their differential circRNA payload. A bioinformatic approach was then utilized to build a circRNA/miRNA/mRNA network. With the aim to demonstrate a dynamic contribution of circRNAs to the sperm epigenetic signature, we verified their modulation as a consequence of an oral amino acid supplementation, efficacious in improving SPZ motility.
- Published
- 2020
30. Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality
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Silvia Fasano, Rosanna Chianese, Gilda Cobellis, Riccardo Pierantoni, Francesco Manfrevola, Teresa Chioccarelli, Veronica Porreca, Chioccarelli, Teresa, Pierantoni, Riccardo, Manfrevola, Francesco, Porreca, Veronica, Fasano, Silvia, Chianese, Rosanna, and Cobellis, Gilda
- Subjects
lcsh:Medicine ,Review ,sperm ,Chromatin remodeling ,03 medical and health sciences ,0302 clinical medicine ,histone post-translational modifications (histone ptms) ,microRNA ,Medicine ,Epigenetics ,human male infertility ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,circular rnas (circrnas) ,lcsh:R ,Translation (biology) ,embryo development ,General Medicine ,spermatogenesis ,Chromatin ,Cell biology ,Histone ,fertilization ,biology.protein ,business ,Homologous recombination ,Spermatogenesis ,030217 neurology & neurosurgery - Abstract
Spermatozoa (SPZ) are motile cells, characterized by a cargo of epigenetic information including histone post-translational modifications (histone PTMs) and non-coding RNAs. Specific histone PTMs are present in developing germ cells, with a key role in spermatogenic events such as self-renewal and commitment of spermatogonia (SPG), meiotic recombination, nuclear condensation in spermatids (SPT). Nuclear condensation is related to chromatin remodeling events and requires a massive histone-to-protamine exchange. After this event a small percentage of chromatin is condensed by histones and SPZ contain nucleoprotamines and a small fraction of nucleohistone chromatin carrying a landascape of histone PTMs. Circular RNAs (circRNAs), a new class of non-coding RNAs, characterized by a nonlinear back-spliced junction, able to play as microRNA (miRNA) sponges, protein scaffolds and translation templates, have been recently characterized in both human and mouse SPZ. Since their abundance in eukaryote tissues, it is challenging to deepen their biological function, especially in the field of reproduction. Here we review the critical role of histone PTMs in male germ cells and the profile of circRNAs in mouse and human SPZ. Furthermore, we discuss their suggested role as novel epigenetic biomarkers to assess sperm quality and improve artificial insemination procedure.
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- 2020
31. Chronic exposure to low dose of bisphenol A impacts on the first round of spermatogenesis via SIRT1 modulation
- Author
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Marika Scafuro, Jacopo Troisi, Loreta Pia Ciuffreda, Maurizio Guida, Rosaria Meccariello, Konrad Urbanek, Liberato Berrino, Donato Cappetta, Riccardo Pierantoni, Antonella De Angelis, Rosanna Chianese, Francesco Rossi, Andrea Viggiano, Silvia Fasano, Grazia Esposito, Chianese, R, Viggiano, A, Urbanek, K, Cappetta, D, Troisi, J, Scafuro, M, Guida, M, Esposito, G, Ciuffreda, Lp, Rossi, F, Berrino, L, Fasano, S, Pierantoni, R, De Angelis, A, Meccariello, R., Rosanna, Chianese, Andrea, Viggiano, Konrad, Urbanek, Donato, Cappetta, Jacopo, Troisi, Marika, Scafuro, Guida, Maurizio, Esposito, MARIA GRAZIA, Loreta Pia Ciuffreda, Francesco, Rossi, Liberato, Berrino, Silvia, Fasano, Riccardo, Pierantoni, Antonella De Angelis, & Rosaria Meccariello, and Urbanek, Konrad Arkadiusz
- Subjects
Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Time Factors ,Offspring ,DNA damage ,lcsh:Medicine ,Down-Regulation ,Apoptosis ,010501 environmental sciences ,medicine.disease_cause ,01 natural sciences ,Gene Expression Regulation, Enzymologic ,Article ,Energy homeostasis ,03 medical and health sciences ,Phenols ,Sirtuin 1 ,Internal medicine ,Testis ,medicine ,Animals ,Endocrine system ,Benzhydryl Compounds ,Rats, Wistar ,lcsh:Science ,Spermatogenesis ,Autocrine signalling ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,Reactive oxygen species ,Multidisciplinary ,Dose-Response Relationship, Drug ,lcsh:R ,Body Weight ,Rats ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,lcsh:Q ,Female ,hormones, hormone substitutes, and hormone antagonists ,Oxidative stress ,DNA Damage - Abstract
Spermatogenesis depends on endocrine, autocrine and paracrine communications along the hypothalamus-pituitary-gonad axis. Bisphenol A (BPA), an estrogen-mimic endocrine disrupting chemical, is an environmental contaminant used to manufacture polycarbonate plastics and epoxy resins with toxic effects for male reproduction. Here we investigated whether the chronic exposure to low BPA doses affects spermatogenesis through the modulation of SIRT1, a NAD+-dependent deacetylase involved in the progression of spermatogenesis, with outcomes on apoptosis, oxidative stress, metabolism and energy homeostasis. BPA exposure via placenta first, and lactation and drinking water later, affected the body weight gain in male offspring at 45 postnatal days and the first round of spermatogenesis, with impairment of blood testis barrier, reactive oxygen species production, DNA damage and decreased expression of SIRT1. The analysis of SIRT1 downstream molecular pathways revealed the increase of acetyl-p53Lys370, γH2AX foci, the decrease of oxidative stress defenses and the higher apoptotic rate in the testis of treated animals, with partial rescue at sex maturation. In conclusion, SIRT1 pathways disruption after BPA exposure can have serious consequences on the first round of spermatogenesis.
- Published
- 2018
32. Expression Patterns of Circular RNAs in High Quality and Poor Quality Human Spermatozoa
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Bruno Ferraro, Carolina Sellitto, Silvia Fasano, Gilda Cobellis, Rosanna Chianese, Marina Migliaccio, Riccardo Pierantoni, Francesco Manfrevola, Teresa Chioccarelli, Chioccarelli, T., Manfrevola, F., Ferraro, B., Sellitto, C., Cobellis, G., Migliaccio, M., Fasano, S., Pierantoni, R., and Chianese, R.
- Subjects
0301 basic medicine ,sperm quality ,Microarray ,Endocrinology, Diabetes and Metabolism ,Motility ,030209 endocrinology & metabolism ,Biology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,circRNAs, embryo development, fertilization, miRNAs, sperm quality, spermatozoa ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,spermatozoa ,microRNA ,medicine ,KEGG ,Original Research ,Messenger RNA ,lcsh:RC648-665 ,Embryogenesis ,embryo development ,Oocyte ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,fertilization ,miRNAs ,circRNAs ,Percoll - Abstract
Circular RNAs (circRNAs) are expressed in human testis and seminal plasma. Until today, there is missing information about a possible payload of circRNAs in human spermatozoa (SPZ). With this in mind, we carried out a circRNA microarray identifying a total of 10.726 transcripts, 28% novel based and 84.6% with exonic structure; their potential contribution in molecular pathways was evaluated by KEGG analysis. Whether circRNAs may be related to SPZ quality was speculated evaluating two different populations of SPZ (A SPZ = good quality, B SPZ = low quality), separated on the basis of morphology and motility parameters, by Percoll gradient. Thus, 148 differentially expressed (DE)-circRNAs were identified and the expression of selected specific SPZ-derived circRNAs was evaluated in SPZ head/tail-enriched preparations, to check the preservation of these molecules during SPZ maturation and their transfer into oocyte during fertilization. Lastly, circRNA/miRNA/mRNA network was built by bioinformatics approach.
- Published
- 2019
33. CircNAPEPLD is expressed in human and murine spermatozoa and physically interacts with oocyte miRNAs
- Author
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Michele Purrello, Rosalia Battaglia, Riccardo Pierantoni, Luca Roberto, Duilia Brex, Bruno Ferraro, Davide Barbagallo, Gilda Cobellis, Francesco Manfrevola, Teresa Chioccarelli, Marco Ragusa, Cinzia Di Pietro, Concetta Ambrosino, Rosanna Chianese, Carolina Sellitto, Silvia Fasano, Ragusa, M, Barbagallo, D, Chioccarelli, T, Manfrevola, F, Cobellis, G, Di Pietro, C, Brex, D, Battaglia, R, Fasano, S, Ferraro, B, Sellitto, C, Ambrosino, C, Roberto, L, Purrello, M, Pierantoni, R, and Chianese, R.
- Subjects
Male ,endocrine system ,Zygote ,media_common.quotation_subject ,Biology ,NAPEPLD, Spermatozoa, ircRNAs, miR-CATCH, miRNAs, reproduction ,reproduction ,03 medical and health sciences ,miR-CATCH ,Mice ,0302 clinical medicine ,microRNA ,Gene expression ,medicine ,Animals ,Humans ,Computer Simulation ,Amino Acid Sequence ,RNA, Messenger ,NAPEPLD ,Molecular Biology ,Gene ,ircRNAs ,030304 developmental biology ,media_common ,0303 health sciences ,urogenital system ,miRNAs ,Spermatozoa ,Cell Biology ,RNA, Circular ,Oocyte ,Cell biology ,MicroRNAs ,medicine.anatomical_structure ,HEK293 Cells ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Eukaryotic Initiation Factor-4A ,Oocytes ,Reproduction ,Function (biology) ,Research Paper ,Signal Transduction - Abstract
Circular RNAs (circRNAs) have a critical role in the control of gene expression. Their function in spermatozoa (SPZ) is unknown to date. Twenty-eight genes, involved in SPZ/testicular and epididymal physiology, were given in circBase database to find which of them may generate circular transcripts. We focused on circNAPEPLDiso1, one of the circular RNA isoforms of NAPEPLD transcript, because expressed in human and murine SPZ. In order to functionally characterize circNAPEPLDiso1 as potential microRNA (miRNA) sponge, we performed circNAPEPLDiso1-miR-CATCH and then profiled the expression of 754 miRNAs, by using TaqMan (R) Low Density Arrays. Among them, miRNAs 146a-5p, 203a-3p, 302c-3p, 766-3p and 1260a (some of them previously shown to be expressed in the oocyte), resulted enriched in circNAPEPLDiso1-miR-CATCHed cell lysate: the network of interactions generated from their validated targets was centred on a core of genes involved in the control of cell cycle. Moreover, computational analysis of circNAPEPLDiso1 sequence also showed its potential translation in a short form of NAPEPLD protein. Interestingly, the expression analysis in murine-unfertilized oocytes revealed low and high levels of circNAPEPLDiso1 and circNAPEPLDiso2, respectively. After fertilization, circNAPEPLDiso1 expression significantly increased, instead circNAPEPLDiso2 expression appeared constant. Based on these data, we suggest that SPZ-derived circNAPEPLDiso1 physically interacts with miRNAs primarily involved in the control of cell cycle; we hypothesize that it may represent a paternal cytoplasmic contribution to the zygote and function as a miRNA decoy inside the fertilized oocytes to regulate the first stages of embryo development. This role is proposed here for the first time.
- Published
- 2019
34. A novel experimental approach for liver analysis in rats exposed to Bisphenol A by means of LC-mass spectrometry and infrared spectroscopy
- Author
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Carla Nicolucci, Nadia Diano, Marika Scafuro, Marianna Portaccio, Rosanna Chianese, Sonia Errico, Rosaria Meccariello, Maria Lepore, Errico, Sonia, Portaccio, Marianna, Nicolucci, Carla, Meccariello, Rosaria, Chianese, Rosanna, Scafuro, Marika, Lepore, Maria, and Diano, Nadia
- Subjects
Male ,Rat liver ,Bisphenol A ,Spectrophotometry, Infrared ,Hepatotoxic effect ,Clinical Biochemistry ,Pharmaceutical Science ,Infrared spectroscopy ,Mass spectrometry ,01 natural sciences ,Analytical Chemistry ,chemistry.chemical_compound ,Phenols ,Tandem Mass Spectrometry ,Metabolic disturbance ,Drug Discovery ,Chemical contaminants ,Animals ,Tissue Distribution ,Benzhydryl Compounds ,Rats, Wistar ,Spectroscopy ,Chromatography ,Spectrometer ,010405 organic chemistry ,Chemistry ,Drug Discovery3003 Pharmaceutical Science ,010401 analytical chemistry ,Bisphenol A exposure ,Rats ,0104 chemical sciences ,Disease Models, Animal ,Liver ,Nucleic acid ,Female ,Chemical and Drug Induced Liver Injury ,Chromatography, Liquid - Abstract
An innovative complementary approach using a liquid chromatographic-mass spectrometer method and infrared spectroscopy is proposed for measuring internal biological exposure to dangerous chemical contaminants and for monitoring biochemical changes in target organs. The proposed methodologies were validated and applied in the case of rats exposed to low-doses of Bisphenol A (BPA). A liquid chromatographic method coupled to a tandem mass spectrometer was used in order to measure BPA concentration in rat livers. BPA was detected at different levels in all liver samples from BPA-treated rats, although the exposure dose was the same in all treated animals, and also from control rats, highlighting the difficulties in eliminating external uncontrolled exposure and the need for internal biological monitoring. Fourier Transform Infrared analysis was applied to detect structural changes occurring in several molecules (lipids, proteins, carbohydrates and nucleic acids) as well as the presence of specific metabolic processes. The spectroscopic analyses clearly demonstrated a different lipid composition more than an evident lipid accumulation and a glycogen accumulation decrease, revealing a metabolic disturbance in livers with a normal histological aspect. These results demonstrated the potential of an integrated approach based on mass spectrometry and infrared spectroscopy to evaluate at an early stage the hepatotoxic effect of BPA exposure in an animal model. This approach can be usefully exploited in all the investigations aimed to provide better information concerning the interrelationships between contaminant exposure, dose, and health effects.
- Published
- 2019
35. Anandamide acts via kisspeptin in the regulation of testicular activity of the frog, Pelophylax esculentus
- Author
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Silvia Fasano, Monica Sirleto, Rosaria Meccariello, Rosanna Chianese, Riccardo Pierantoni, Vincenza Ciaramella, and Teresa Chioccarelli
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Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Cannabinoid receptor ,Polyunsaturated Alkamides ,medicine.drug_class ,Arachidonic Acids ,Gonadotropin-releasing hormone ,Biology ,Biochemistry ,Amidohydrolases ,03 medical and health sciences ,chemistry.chemical_compound ,Aromatase ,Receptors, Gonadotropin ,Endocrinology ,Kisspeptin ,Piperidines ,Internal medicine ,Testis ,medicine ,Animals ,Testosterone ,Diencephalon ,Receptor ,Molecular Biology ,Kisspeptins ,Estradiol ,Rana esculenta ,Anandamide ,Endocannabinoid system ,030104 developmental biology ,chemistry ,Pyrazoles ,lipids (amino acids, peptides, and proteins) ,Rimonabant ,Gonadotropin ,hormones, hormone substitutes, and hormone antagonists ,Endocannabinoids - Abstract
In the frog Pelophylax esculentus, the endocannabinoid anandamide (AEA) modulates Gonadotropin Releasing Hormone (GnRH) system in vitro and down-regulates steroidogenic enzymes in vivo. Thus, male frogs were injected with AEA ± SR141716A, a cannabinoid receptor 1 (CB1) antagonist, to evaluate possible effects on GnRH and Kiss1/Gpr54 systems, gonadotropin receptors and steroid levels. In frog diencephalons, AEA negatively affected both GnRH and Kiss1/Gpr54 systems. In testis, AEA induced the expression of gonadotropin receptors, cb1, gnrh2 and gnrhr3 meanwhile reducing gnrhr2 mRNA and Kiss1/Gpr54 proteins. Furthermore, aromatase (Cyp19) expression increased in parallel to testosterone decrease and estradiol increase. In vitro treatment of testis with AEA revealed direct effects on Cyp19 and induced the expression of the AEA-degrading enzyme Faah. Lastly, AEA effects on Faah were counteracted by the antiestrogen ICI182780, indicating estradiol mediated effect. In conclusion, for the first time we show in a vertebrate that AEA regulates testicular activity through kisspeptin system.
- Published
- 2016
36. Introductory Chapter: Spermatozoa - Facts and Perspectives
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Rosaria Meccariello and Rosanna Chianese
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Biology - Published
- 2018
37. Spermatozoa - Facts and Perspectives
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Rosanna Chianese and Rosaria Meccariello
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Gynecology ,medicine.medical_specialty ,business.industry ,Anatomy & histology ,Medicine ,business ,medicine.disease ,Male infertility - Published
- 2018
38. Impact of dietary fats on brain functions
- Author
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Rosaria Meccariello, Giangennaro Coppola, Marco Fiore, Riccardo Pierantoni, Marika Scafuro, Sophie Layé, Francesca Felicia Operto, Roberto Coccurello, Silvia Fasano, Andrea Viggiano, Rosanna Chianese, University of Campania, Partenaires INRAE, Institute of Cell Biology and Neurobiology, National Research Council (CNR), Università degli Studi di Salerno (UNISA), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Università degli studi di Napoli Federico II, Chianese, R, Coccurello, R, Viggiano, A, Scafuro, M, Fiore, M, Coppola, G, Operto, Ff, Fasano, S, Layé, S, Pierantoni, R, and Meccariello, R.
- Subjects
0301 basic medicine ,nutrient sensing ,[SDV]Life Sciences [q-bio] ,ketogenic diets ,Disease ,Nutrient sensing ,Biology ,Neuroprotection ,leptin ,Article ,kisspeptin ,reproduction ,03 medical and health sciences ,metabolic sensors ,0302 clinical medicine ,Kisspeptin ,fat ,microbiota ,Animals ,Humans ,Pharmacology (medical) ,endocannabinoids ,hypothalamus ,Pharmacology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Leptin ,Brain ,Cognition ,General Medicine ,Endocannabinoid system ,Dietary Fats ,Gastrointestinal Microbiome ,Psychiatry and Mental health ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,GnRH ,PUFAs ,diet ,epilepsy ,ghrelin ,neuroprotection ,030104 developmental biology ,Neurology ,microbiota brain ,Ghrelin ,Neurology (clinical) ,Neuroscience ,030217 neurology & neurosurgery - Abstract
International audience; Background: Adequate dietary intake and nutritional status have important effects on brain functions and on brain health. Energy intake and specific nutrients excess or deficiency from diet differently affect cognitive processes, emotions, behaviour, neuroendocrine functions and synaptic plasticity with possible protective or detrimental effects on neuronal physiology. Lipids, in particular, play structural and functional roles in neurons. Here the importance of dietary fats and the need to understand the brain mechanisms activated by peripheral and central metabolic sensors. Thus, the manipulation of lifestyle factors such as dietary interventions may represent a successful therapeutic approach to maintain and preserve brain health along lifespan. Methods: This review aims at summarizing the impact of dietary fats on brain functions. Results: Starting from fat consumption, nutrient sensing and food-related reward, the impact of gut-brain communications will be discussed in brain health and disease. A specific focus will be on the impact of fats on the molecular pathways within the hypothalamus involved in the control of reproduction via the expression and the release of Gonadotropin-Releasing Hormone. Lastly, the effects of specific lipid classes such as polyunsaturated fatty acids and of the "fattest" of all diets, commonly known as "ketogenic diets", on brain functions will also be discussed. Conclusion: Despite the knowledge of the molecular mechanisms is still a work in progress, the clinical relevance of the manipulation of dietary fats is well acknowledged and such manipulations are in fact currently in use for the treatment of brain diseases.
- Published
- 2018
39. Bisphenol A in reproduction: epigenetic effects
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Rosaria Meccariello, Sean M. Richards, Marika Scafuro, Silvia Fasano, Jacopo Troisi, Maurizio Guida, Rosanna Chianese, Riccardo Pierantoni, Chianese, R, Troisi, J, Richards, S, Scafuro, M, Fasano, S, Guida, M, Pierantoni, R, Meccariello, R., Chianese, Rosanna, Troisi, Jacopo, Richards, Sean, Scafuro, Marika, Fasano, Silvia, Guida, Maurizio, Pierantoni, Riccardo, and Meccariello, Rosaria
- Subjects
Male ,0301 basic medicine ,endocrine system ,Offspring ,media_common.quotation_subject ,medicine.medical_treatment ,Physiology ,Endocrine Disruptors ,010501 environmental sciences ,Biology ,01 natural sciences ,Biochemistry ,Epigenesis, Genetic ,gametogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,Bisphenol A ,Phenols ,Testis ,Drug Discovery ,medicine ,Animals ,Humans ,Epigenetics ,Benzhydryl Compounds ,Endocrine disrupting chemicals ,0105 earth and related environmental sciences ,media_common ,Pharmacology ,fertility ,In vitro fertilisation ,epigenetics ,urogenital system ,transgenerational effects ,Ovary ,Organic Chemistry ,embryo development ,Environmental exposure ,Embryo, Mammalian ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Molecular Medicine ,Gamete ,Female ,Reproduction ,Spermatogenesis ,Toxicant - Abstract
Background: Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the manufacture of polycarbonate plastic and epoxy resin to produce a multitude of consumer products, food and drink containers, and medical devices. BPA is similar to estradiol in structure and thus interferes in steroid signalling with different outcomes on reproductive health depending on doses, life stage, mode, and timing of exposure. In this respect, it has an emerging and controversial role as a "reproductive toxicant" capable of inducing short and long-term effects including the modulation of gene expression through epigenetic modification (i.e. methylation of CpG islands, histone modifications and production of non-coding RNA) with direct and trans-generational effects on exposed organisms and their offspring, respectively. Objective: This review provides an overview about BPA effects on reproductive health and aims to summarize the epigenetic effects of BPA in male and female reproduction. Results: BPA exerts epigenetic effects in both male and female reproduction. In males, BPA affects spermatogenesis and sperm quality and possible trans-generational effects on the reproductive ability of the offspring. In females, BPA affects ovary, embryo development, and gamete quality for successful in vivo and in vitro fertilization (IVF). Conclusion: The exact mechanisms of BPA-mediated effects in reproduction are not fully understood; however, the environmental exposure to BPA - especially in fetal and neonatal period - deserves attention to preserve the reproductive ability in both sexes and to reduce the epigenetic risk for the offspring.
- Published
- 2018
40. Antitumor efficacy of Kisspeptin in human malignant mesothelioma cells
- Author
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Roberto Bianco, Floriana Morgillo, Sandro Cosconati, Stefano Tomassi, Fortunato Ciardiello, Carminia Maria Della Corte, Concetta Di Mauro, Rosaria Meccariello, Teresa Troiani, Salvatore Di Maro, Riccardo Pierantoni, Vincenza Ciaramella, Rosanna Chianese, Erika Martinelli, Ciaramella, V, Della Corte, Cm, Di Mauro, C, Tomassi, S, Di Maro, S, Troiani, T, Martinelli, E, Bianco, R, Cosconati, S, Pierantoni, R, Meccariello, R, Chianese, R, Ciardiello, F, Morgillo, F., and DELLA CORTE, Carminia Maria
- Subjects
0301 basic medicine ,Metastatic phenotype ,Tumor cells ,Metastasi ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Kisspeptin ,medicine ,metastasis ,Mesothelioma ,business.industry ,Metastasis formation ,EMT ,KiSS1 ,medicine.disease ,030104 developmental biology ,Oncology ,mesothelioma ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,biomarker ,business ,After treatment ,Research Paper - Abstract
// Vincenza Ciaramella 1 , Carminia Maria Della Corte 1 , Concetta Di Mauro 2 , Stefano Tomassi 3 , Salvatore Di Maro 3 , Teresa Troiani 1 , Erika Martinelli 1 , Roberto Bianco 2 , Sandro Cosconati 3 , Riccardo Pierantoni 4 , Rosaria Meccariello 5 , Rosanna Chianese 4 , Fortunato Ciardiello 1 and Floriana Morgillo 1 1 Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale “F. Magrassi”, Universita degli Studi della Campania Luigi Vanvitelli, Naples, Italy 2 Oncologia Medica, Dipartimento di Medicina Clinica e Chirurgia, Universita degli Studi di Napoli “Federico II”, Naples, Italy 3 DISTABIF, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy 4 Dipartimento di Medicina Sperimentale sez ‘F. Bottazzi’, Universita degli Studi della Campania Luigi Vanvitelli, Naples, Italy 5 Dipartimento di Scienze Motorie e del Benessere, Universita di Napoli Parthenope, Napoli, Italy Correspondence to: Floriana Morgillo, email: florianamorgillo@yahoo.com Keywords: mesothelioma; KiSS1; biomarker; metastasis; EMT Received: February 03, 2018 Accepted: February 27, 2018 Published: April 10, 2018 ABSTRACT Purpose: Kisspeptin signaling, via its receptors GPR54, could be an essential players in the inhibition of mesothelioma progression, invasion and metastasis formation. The loss of KiSS1 by tumor cells has been associated with a metastatic phenotype but the mechanistic insights of this process are still unknown. Experimental design: The blockade of the metastatic process at early stage is a hot topic in cancer research. We studied the role of KiSS1 on proliferation, invasiveness, migration abilities of mesothelioma cell lines focusing on the effect on epithelial-to-mesenchymal transition (EMT). Results: Treatment with the KiSS1 peptide or with a synthesis peptide with longer half-life, the FTM080, significantly inhibited cell proliferation, migration and invasion of mesothelioma cell lines; the same treatment reduced the activity of MMP-2 and MMP-9 determining consequently a marked reduction in the invasiveness of primary tumors and metastases. Thespecificexpression of EMT markers, as E-caderin, Vimentin, Slug and Snail, suggested the inhibition of EMT after treatment with KiSS1 as well as the preservation of epithelial components. Conclusion: Our results support anti-proliferative effect of KiSS1 in cancer cells and suggest that targeting the KiSS1/GPR54 system may represent a novel therapeutic approach for mesothelioma.
- Published
- 2018
41. Kisspeptin regulates steroidogenesis and spermiation in anuran amphibian
- Author
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Rosanna Chianese, Riccardo Pierantoni, Vincenza Ciaramella, Silvia Fasano, Rosaria Meccariello, Chianese, R, Ciaramella, V, Fasano, S, Pierantoni, R, and Meccariello, R.
- Subjects
Male ,0301 basic medicine ,Embryology ,medicine.medical_specialty ,Biology ,03 medical and health sciences ,Endocrinology ,Kisspeptin ,In vivo ,Internal medicine ,Paracrine Communication ,medicine ,Animals ,Humans ,Testosterone ,Spermatogenesis ,Receptor ,Kisspeptins ,Sertoli Cells ,Dose-Response Relationship, Drug ,Estradiol ,Rana esculenta ,Obstetrics and Gynecology ,Cell Biology ,Sertoli cell ,Spermatozoa ,Sperm ,Autocrine Communication ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,Connexin 43 ,Ex vivo ,Receptors, Kisspeptin-1 ,Signal Transduction - Abstract
Kisspeptin (Kp) system has a recognized role in the control of gonadotropic axis, at multiple levels. Recently, a major focus of research has been to assess any direct activity of this system on testis physiology. Using the amphibian anuran,Pelophylax esculentus, as animal model, we demonstrate – for the first time in non-mammalian vertebrate – that testis expresses both Kiss-1 and Gpr54 proteins during the annual sexual cycle and thatex vivo17B-estradiol (E2, 10−6 M) increases both proteins over control group. Since the interstitium is the main site of localization of both ligand and receptor, its possible involvement in the regulation of steroidogenesis has been evaluated byex vivotreatment of testis pieces with increasing doses of Kp-10 (10−9–10−6 M). Treatments have been carried out in February – when a new wave of spermatogenesis occurs – and affect the expression of key enzymes of steroidogenesis inducing opposite effects on testosterone and estradiol intratesticular levels. Morphological analysis of Kp-treated testes reveals higher number of tubules with spermatozoa detached from Sertoli cells than control group and the expression of connexin 43, the main junctional protein in testis, is deeply affected by the treatment. In spite of the effects on spermatozoa observedex vivo,in vivoadministration of Kp-10 has been unable to induce sperm release in cloacal fluid. In conclusion, we demonstrate Kp-10 effects on steroidogenesis with possible involvement in the balance between testosterone and estradiol levels, and report new Kp-10 activities on spermatozoa–Sertoli cell interaction.
- Published
- 2017
42. Cannabinoids in Health and Disease
- Author
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Rosaria Meccariello and Rosanna Chianese
- Subjects
medicine.medical_specialty ,business.industry ,Family medicine ,Medicine ,Disease ,Complementary medicine ,business ,Biomedical sciences - Published
- 2016
43. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells
- Author
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Gilda Cobellis, Silvia Fasano, Rosaria Meccariello, Riccardo Pierantoni, Teresa Chioccarelli, Rosanna Chianese, Cobellis, Gilda, Meccariello, R, Chianese, Rosanna, Chioccarelli, Teresa, Fasano, Silvia, and Pierantoni, Riccardo
- Subjects
0301 basic medicine ,medicine.medical_specialty ,endocrine system ,steroidogenesis ,Cannabinoid receptor ,Somatic cell ,Spermiogenesis ,Endocrinology, Diabetes and Metabolism ,Mini Review ,030209 endocrinology & metabolism ,Leydig cells ,Steroid biosynthesis ,Biology ,testis ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,CB1, endocannabinoids, Leydig cells, steroidogenesis, spermatogenesis, testis ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,endocannabinoids ,lcsh:RC648-665 ,Leydig cell ,Leydig cell differentiation ,Endocannabinoid system ,CB1 ,spermatogenesis ,030104 developmental biology ,medicine.anatomical_structure ,lipids (amino acids, peptides, and proteins) ,Spermatogenesis - Abstract
Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis.
- Published
- 2016
44. Kisspeptins, estrogens and male fertility
- Author
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Teresa Chioccarelli, Marina Migliaccio, Rosanna Chianese, Silvia Fasano, Rosaria Meccariello, Riccardo Pierantoni, Vincenza Ciaramella, Gilda Cobellis, Chianese, Rosanna, Cobellis, Gilda, Chioccarelli, Teresa, Ciaramella, Vincenza, Migliaccio, Marina, Fasano, Silvia, Pierantoni, Riccardo, and Meccariello, Rosaria
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,endocrine system ,Gonadotropin-releasing hormone ,Biology ,Biochemistry ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,Paracrine signalling ,Hormone Antagonists ,Kisspeptin ,Kisspeptins ,Internal medicine ,Testis ,Drug Discovery ,medicine ,Animals ,Humans ,Autocrine signalling ,Pharmacology ,Kiss1, Gpr54, estrogens, ER, ER, GPR30, testis, spermatogenesis ,Reproduction ,Organic Chemistry ,Estrogens ,Spermatozoa ,030104 developmental biology ,Endocrinology ,Receptors, Estrogen ,Molecular Medicine ,GPER ,Hypogonadotrophic hypogonadism ,hormones, hormone substitutes, and hormone antagonists ,Receptors, Kisspeptin-1 ,Hormone - Abstract
Background: The control of male fertility requires accurate endocrine, paracrine and autocrine communications along the hypothalamus-pituitary-gonad (HPG) axis. In this respect, the possible interplay between upcoming/classical modulators of reproductive functions deserves attention in that may be a successful tool for the future exploitation of new potential therapeutic targets in the treatment of fertility disorders. Methods: In this review we will discuss upcoming data concerning the role of kisspeptins, the products of the Kiss1 gene, and estrogens - classically considered as female hormones - as well as their possible interplay in testis. Results: Kisspeptins, via the activation of kisspeptin receptor Gpr54 represent the main gatekeeper of the hypothalamic Gonadotropin Releasing Hormone (GnRH) centrally modulating the onset and the maintaining of reproductive functions. As a consequence, the loss of kisspeptin signalling causes hypogonadotrophic hypogonadism in humans and animal models. In spite of the well recognized functions at hypothalamic levels, recent data strongly support direct production and activity of kisspeptin in testis and its involvement in the control of Leydig cells, germ cells progression and sperm functions. Similarly, estrogens exhibit high impact on proliferative/apoptotic/differentiative events in testis, thus resulting as local key modulators for the production - but also for the release, the transport and the maturation - of high quality spermatozoa. Conclusion: This review summarizes the upcoming data from experimental models and humans concerning the testicular activity of kisspeptins and estrogens to preserve male fertility. Mutual enhancement of kisspeptin and estradiol signalling for the progression of spermatogenesis has also been discussed.
- Published
- 2016
45. Anandamide regulates the expression of GnRH1, GnRH2, and GnRH-Rs in frog testis
- Author
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Rosanna Chianese, Rosaria Meccariello, Silvia Fasano, Riccardo Pierantoni, Vincenza Ciaramella, Donatella Scarpa, Chianese, Rosanna, Ciaramella, V, Scarpa, D, Fasano, Silvia, Pierantoni, Riccardo, and Meccariello, R.
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Polyunsaturated Alkamides ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,gonadotropin-releasing hormone receptor ,Arachidonic Acids ,Gonadotropin-releasing hormone ,Biology ,Testicle ,Gonadotropin-Releasing Hormone ,chemistry.chemical_compound ,Piperidines ,Receptor, Cannabinoid, CB1 ,Salientia ,Physiology (medical) ,Internal medicine ,Testis ,Phospholipase D ,medicine ,Animals ,Spermatogenesis ,Rana esculenta ,Anandamide ,biology.organism_classification ,Endocannabinoid system ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Pyrazoles ,GRENOUILLE ,lipids (amino acids, peptides, and proteins) ,Seasons ,Cannabinoid ,Rimonabant ,Receptors, LHRH ,hormones, hormone substitutes, and hormone antagonists ,Endocannabinoids ,Hormone - Abstract
Anandamide regulates the expression of GnRH1, GnRH2, and GnRH-Rs in frog testis. Am J Physiol Endocrinol Metab 303: E475–E487, 2012. First published June 5, 2012; doi:10.1152/ajpendo.00086.2012.— Gonadotropin-releasing hormone (either GnRH1 or GnRH2) exerts a local activity in vertebrate testis, including human testis. Relationships between endocannabinoid (eCB) and GnRH systems in gonads have never been elucidated in any species so far. To reveal a cross-talk between eCBs and GnRH at testicular level, we characterized the expression of GnRH (GnRH1 and GnRH2) as well as GnRH receptor (GnRH-R1, -R2, and -R3) mRNA in the testis of the anuran amphibian Rana esculenta during the annual sexual cycle; furthermore, the corresponding transcripts were localized inside the testis by in situ hybridization. The possible endogenous production of the eCB, anandamide (AEA), was investigated in testis by analyzing the expression of its biosynthetic enzyme, Nape-pld. Incubations of testis pieces with AEA were carried out in the postreproductive period (June) and in February, when a new spermatogenetic wave takes place. In June, AEA treatment significantly decreased GnRH1 and GnRH-R2 mRNA, stimulated the transcription of GnRH2 and GnRH-R1, and did not affect GnRH-R3 expression. In February, AEA treatment upregulated GnRH2 and GnRH-R3 mRNA, downregulated GnRH-R2, and did not affect GnRH1 and GnRH-R1 expression. These effects were mediated by type 1 cannabinoid receptor (CB1) since they were fully counteracted by SR141716A (Rimonabant), a selective CB1 antagonist. In conclusion, eCB system modulates GnRH activity in frog testis during the annual sexual cycle in a stagedependent fashion.
- Published
- 2012
46. Expression and localization of the deubiquitinating enzyme mUBPy in wobbler mouse testis during spermiogenesis
- Author
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Gilda Cobellis, Riccardo Pierantoni, Donatella Scarpa, Rosaria Meccariello, Giovanna Berruti, Silvia Fasano, Rosanna Chianese, Chianese, R., Scarpa, D., Berruti, G., Cobellis, G., Pierantoni, R., Fasano, S., and Meccariello, R.
- Subjects
Male ,Spermiogenesis ,Gene Expression ,Biology ,Mice ,Mice, Neurologic Mutants ,Endocrinology ,Western blot ,Endopeptidases ,Testis ,medicine ,Animals ,HSP70 Heat-Shock Proteins ,RNA, Messenger ,Northern blot ,Spermatogenesis ,Acrosome ,Messenger RNA ,Endosomal Sorting Complexes Required for Transport ,medicine.diagnostic_test ,Immunohistochemistry ,Spermatids ,Sperm ,Molecular biology ,Cytoplasm ,Mutation ,Animal Science and Zoology ,Ubiquitin Thiolesterase - Abstract
Mouse ubiquitin-specific processing protease (mUBPy) is a deubiquitinating enzyme highly expressed in both brain and testis. In testis, it interacts with the DnaJ protein, MSJ-1; both mUBPy and MSJ-1 are located on the cytoplasmic surface of the developing acrosome and in the centrosomal region during spemiogenesis. Present data show the first appearance in testis of mUbpy mRNA and protein at 10 days post-partum (d.p.p.). In addition, to investigate on a possible role of mUBPy in sperm formation, we took advantage of mutant wr/wr (wobbler) mice characterized by male infertility, which is likely due to the lack of a real, functional acrosome. RT-PCR and Northern blot analyses show that mUbpy is up-regulated in adult wobbler testis. Furthermore, in wild-type testis mUBPy protein is primarily detected by Western blot in the soluble (cytosolic/nuclear) fraction during the first round of spermatogenesis and in the adult. By contrast, mUBPy is primarily detected in membranous/insoluble protein fraction when wobbler phenotype is clearly shown (30 d.p.p.) and in adult wobbler testis. By immunohistochemistry, whereas in wild-type animals mUBPy marks the profile of the acrosomic vesicle in differentiating spermatids, in wobbler mice only a detergent pre-treatment procedure allows to detect mUBPy immunoreactivity, which results in diffuse spotted granules inside the cytoplasm and around the nuclear shape. In conclusion, in wobbler testis expression of mUbpy is up-regulated, while a differential sorting of the protein characterizes wobbler spermatids where acrosome formation is impaired.
- Published
- 2010
47. Structure of msj-1 gene in mice and humans: A possible role in the regulation of male reproduction
- Author
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Gilda Cobellis, Fiorella Altruda, F. Di Cunto, Donatella Scarpa, Ivana Zucchetti, Giovanna Berruti, Silvia Fasano, Riccardo Pierantoni, Rosaria Meccariello, Rosanna Chianese, R. De Santis, Meccariello, R, Berruti, G, Chianese, Rosanna, DE SANTIS, R, DI CUNTO, F, Scarpa, D, Cobellis, Gilda, Zucchetti, I, Altruda, F, Pierantoni, Riccardo, and Fasano, Silvia
- Subjects
Male ,DnaJ protein ,Mouse ,Molecular Sequence Data ,Inbred Strains ,Mice, Inbred Strains ,Nerve Tissue Proteins ,Biology ,DNAJ Protein ,Promoter Regions ,Mice ,Endocrinology ,Genetic ,Heat shock protein ,Testis ,Animals ,Humans ,Coding region ,Amino Acid Sequence ,msj-1 ,Promoter Regions, Genetic ,Gene ,Peptide sequence ,Genetics ,Base Sequence ,UDP glucuronosyltransferase ,Reproduction ,Intron ,Chromosome ,HSP40 Heat-Shock Proteins ,Spermatozoa ,Human ,Acrosome ,Molecular Chaperones ,Animal Science and Zoology ,Human genome - Abstract
Msj-1 gene encodes a DnaJ protein highly expressed in spermatids and spermatozoa of both rodents and amphibians, possibly involved in vesicle fusion and protein quality control by means of interaction with heat shock proteins. We isolated and characterized the entire murine msj -1 gene and searched for putative msj-1 -like genes into the human genome. Furthermore, ultrastructural localization of MSJ-1 was analyzed in mouse germ cells by immunogold electron microscopy. The analysis of murine msj-1 genomic sequence reveals that it is an intron less gene. Putative promoter region was predicted within the 600 bp upstream the transcription start site. In mouse, msj-1 maps on chromosome 1, into an intronic region of UDP glucuronosyl-transferase 1 family cluster. At ultrastructural level, MSJ-1 marks the developing acrosomic vesicle and the sperm centriolar region. A blast search against the human genome database revealed two closed regions ( Ha and Hb ) on human chromosome 2 having high nucleotide identity with murine msj-1 coding region. Similarly to mouse, in human both regions map into an intronic region of UDP glycosyl-transferase 1 family polypeptide A cluster ( ugt1a @). A significant ORF encoding a putative DnaJ protein of 145 aa was predicted from Ha . Finally, expression analysis, conducted by RT-PCR in human sperm cells, demonstrated that Ha mRNA is effectively present in humans; by Western blot, a specific MSJ-1 band of approximately 30 kDa was detected in human sperm. Taken together, these data suggest that msj-1 gene might be conserved among vertebrates and might exert fundamental functions in reproduction.
- Published
- 2008
48. UBPy/MSJ-1 system during male germ cell progression in the frog, Rana esculenta
- Author
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Gilda Cobellis, Giovanna Berruti, Silvia Fasano, Riccardo Pierantoni, Rosaria Meccariello, Donatella Scarpa, Rosanna Chianese, Meccariello, R, Chianese, Rosanna, Scarpa, Donatella, Berruti, G, Cobellis, Gilda, Pierantoni, Riccardo, and Fasano, Silvia
- Subjects
Male ,Amphibian ,endocrine system ,Blotting, Western ,Immunocytochemistry ,DNAJ Protein ,Settore BIO/06 - Anatomia Comparata e Citologia ,Endocrinology ,Western blot ,biology.animal ,Endopeptidases ,medicine ,Animals ,Spermatogenesis ,reproductive and urinary physiology ,Endosomal Sorting Complexes Required for Transport ,biology ,medicine.diagnostic_test ,urogenital system ,Rana esculenta ,HSP40 Heat-Shock Proteins ,Molecular biology ,Sperm ,Blot ,Germ Cells ,medicine.anatomical_structure ,de-ubiquitinating enzynie ,testis ,spermatogenesis ,frog ,Animal Science and Zoology ,Ubiquitin Thiolesterase ,Germ cell - Abstract
mUBPy (mouse ubiquitin specific processing protease) is a de-ubiquitinating enzyme expressed in mouse testis and brain. In testis, it interacts with the DnaJ protein MSJ-1 (mouse sperm cell specific DnaJ first homologue), a molecular chaperone expressed in spermatids and spermatozoa. Since MSJ-1 is conserved among vertebrates, to demonstrate an evolutionarily conserved function of UBPy/MSJ-1 system, we assayed mUBPy presence in the anuran amphibian, the frog, Rana esculenta, during the annual sexual cycle. By Western blot we have detected a specific signal of 126 kDa in testis and isolated spermatozoa. During the annual sexual cycle, the signal gradually increases as soon as spermatogenesis resumes after the winter stasis. Using immunocytochemistry, we have localized the protein in spermatids and spermatozoa. In conclusion, UBPy/MSJ-1 system is available in R. esculenta testis suggesting a conserved fundamental function in spermatogenesis and sperm formation.
- Published
- 2007
49. Cloning of type 1 cannabinoid receptor in Rana esculenta reveals differences between genomic sequence and cDNA
- Author
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Gilda Cobellis, Riccardo Pierantoni, Silvia Fasano, Rosanna Chianese, and Rosaria Meccariello
- Subjects
chemistry.chemical_classification ,Genetics ,Sequence alignment ,Cell Biology ,Biology ,Biochemistry ,Amino acid ,genomic DNA ,chemistry ,Complementary DNA ,GenBank ,Synonymous substitution ,Molecular Biology ,Gene ,Peptide sequence - Abstract
The endocannabinoid system is a conserved system involved in the modulation of several physiologic processes, from the activity of the central nervous system to reproduction. Type 1 cannabinoid receptor (CNR1) cDNA was cloned from the brain and testis of the anuran amphibian, the frog Rana esculenta. Nucleotide identity ranging from 62.6% to 81.9% is observed among vertebrates. The reading frame encoded a protein of 462 amino acids (FCNR1) with all the properties of a membrane G-coupled receptor. Alignments of FCNR1 with those of other vertebrates revealed amino acid identity ranging from 61.9% to 88.1%; critical domains for CNR1 functionality were conserved in the frog. As nucleotide differences of cnr1 cDNA were observed in brain and testis, the genomic sequence of the cnr1 gene was also determined in the same tissue preparations. Nucleotide changes in codons 5, 30, 70, 186, 252 and 408 were observed when cDNA and genomic DNA were compared; the nucleotide differences did not affect the predicted amino acid sequences, except for changes in codons 70 and 408. Interestingly, the predicted RNA folding was strongly affected by different nucleotide sequences. Comparison of cnr1 mRNA sequences available in GenBank with the corresponding genomic sequences revealed that also in human, rat, zebrafish and pufferfish, nucleotide changes between mRNA and genomic sequences occurred. Furthermore, amino acid sequences deduced from both mRNA and the genome were compared among vertebrates, and also in pufferfish the nucleotide changes corresponded to modifications in the amino acid sequence. The present results indicate for the first time that changes in nucleotides may occur in cnr1 mRNA maturation and that this phenomenon might not be restricted to the frog.
- Published
- 2007
50. Expression Analysis of Gnrh1 and Gnrhr1 in Spermatogenic Cells of Rat
- Author
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Rosanna Chianese, Paolo Pariante, Silvia Fasano, Rosaria Meccariello, Riccardo Pierantoni, Vincenza Ciaramella, Ciaramella, Vincenza, Chianese, Rosanna, Pariante, Paolo, Fasano, Silvia, Pierantoni, Riccardo, and Meccariello, Rosaria
- Subjects
medicine.medical_specialty ,endocrine system ,lcsh:RC648-665 ,Article Subject ,Endocrine and Autonomic Systems ,Somatic cell ,urogenital system ,Endocrinology, Diabetes and Metabolism ,GNRHR ,Gonadotropin-releasing hormone ,In situ hybridization ,Biology ,Sertoli cell ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,medicine ,Receptor ,Spermatogenesis ,Gametogenesis ,hormones, hormone substitutes, and hormone antagonists ,Research Article - Abstract
Hypothalamic Gonadotropin Releasing Hormone (GnRH),viaGnRH receptor (GnRHR), is the main actor in the control of reproduction, in that it induces the biosynthesis and the release of pituitary gonadotropins, which in turn promote steroidogenesis and gametogenesis in both sexes. Extrabrain functions of GnRH have been extensively described in the past decades and, in males, local GnRH activity promotes the progression of spermatogenesis and sperm functions at several levels. The canonical localization ofGnrh1andGnrhr1mRNA is Sertoli and Leydig cells, respectively, but ligand and receptor are also expressed in germ cells. Here, we analysed the expression rate ofGnrh1andGnrhr1in rat testis (180 days old) by quantitative real-time PCR (qPCR) and byin situhybridization we localizedGnrh1andGnrhr1mRNA in different spermatogenic cells of adult animals. Our data confirm the testicular expression ofGnrh1and ofGnrhr1in somatic cells and provide evidence that their expression in the germinal compartment is restricted to haploid cells. In addition, not only Sertoli cells connected to spermatids in the last steps of maturation but also Leydig and peritubular myoid cells expressGnrh1.
- Published
- 2015
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