A5044571904- Sperm and Testicular Function
- Effects and risks of endocrine disrupting chemicals
- Reproductive Biology and Fertility
- Sexual Differentiation and Disorders
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Birth, Development, and Health
- Testicular diseases and treatments
- Estrogen and related hormone effects
- Retinoids in leukemia and cellular processes
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Carcinogens and Genotoxicity Assessment
- TGF-β signaling in diseases
- Urological Disorders and Treatments
- Hypothalamic control of reproductive hormones
- Reproductive System and Pregnancy
- Pluripotent Stem Cells Research
- Metabolism and Genetic Disorders
- Hormonal and reproductive studies
- Toxic Organic Pollutants Impact
- Pregnancy and preeclampsia studies
- DNA Repair Mechanisms
- Pharmaceutical studies and practices
- Sarcoma Diagnosis and Treatment
Université Paris Cité
2014-2024
CEA Paris-Saclay - Etablissement de Fontenay-aux-roses
2011-2022
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2012-2021
CEA Paris-Saclay
2016-2021
Sorbonne Paris Cité
2011-2021
Université Paris-Saclay
2005-2021
Sorbonne Université
2021
Inserm
2010-2019
Institut de Radiobiologie Cellulaire et Moléculaire
2006-2018
Stabilité Génétique, Cellules Souches et Radiations
2010-2018
BackgroundSeveral studies have described an increasing frequency of male reproductive disorders, which may a common origin in fetal life and are hypothesized to be caused by endocrine disruptors. Phthalate esters represent class environmental endocrine-active chemicals known disrupt development the tract decreasing testosterone production rat.ObjectivesUsing organ culture system we developed previously, investigated effects on human testis one phthalate—mono-2-ethylhexyl phthalate (MEHP)—an...
Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for health of axons brain function. However, there no efficient treatment stimulating myelin repair, current therapies are limited anti-inflammatory agents. Males less likely develop multiple sclerosis than females, but often have more severe disease course reach disability milestones at an earlier age these observations spurred interest potential...
The initiation of meiosis is crucial to fertility. While extensive studies in rodents have enhanced our understanding this process, human fetal ovary are lacking. We used RT–PCR and immunohistochemistry investigate expression meiotic factors ovaries from 6 15 weeks post fertilization (wpf) developed an organ culture model study the meiosis. observed first cells at 11 wpf, when STRA8, SPO11 DMC1 expressed. In culture, 10 wpf maintained by addition calf serum. Meiosis stimulated, compared with...
Meiotic recombination is a mandatory process for sexual reproduction. We identified protein specifically implicated in meiotic homologous that we named: meiosis specific with OB domain (MEIOB). This conserved among metazoan species and contains single-strand DNA binding sites similar to those of RPA1. Our studies vitro revealed both recombinant endogenous MEIOB can be retained on DNA. Those vivo demonstrated the expression Meiob early germ cells co-localization RPA chromosome axes....
In addition to playing a fundamental role in very diverse processes such as vision and the growth differentiation of numerous types cell, vitamin A (retinol) its principal biologically active derivative, retinoic acid, are clearly involved regulation testicular functions rodents. An excess leads lesions spermatogenetic disorders, deficiency induces early cessation spermatogenesis adversely affects testosterone secretion. Furthermore, mice mutant for acid alpha receptors retinoid X beta...
AbstractDuring mouse fetal development, meiosis is initiated in female germ cells only, with male undergoing mitotic arrest. Retinoic acid (RA) degraded by Cyp26b1 the embryonic testis but not ovary where it initiates mitosis/meiosis transition. However role of RA status cell proliferation has been elucidated. As expected, using organ cultures, we observed that addition 11.5 days post-conception (dpc) testes induced Stra8 expression and meiosis. Surprisingly, 13.5 dpc although did promote On...
BackgroundCadmium (Cd) is a common environmental pollutant and major constituent of tobacco smoke. Adverse effects this heavy metal on reproductive function have been identified in adults; however, no studies examined its human organs during development.ObjectivesUsing our previously developed organ culture system, we investigated the cadmium chloride gonads at beginning fetal life, critical stage development function.MethodsHuman were recovered first trimester (7–11 weeks postconception)...
Endocrine disruptors (ED) have been incriminated in the current increase of male reproductive alterations. Bisphenol A (BPA) is a widely used weak estrogenic environmental ED and it debated whether BPA concentrations within average internal exposure are toxic. In present study we investigated effects 10−12 to 10−5 M on fetal Leydig cell function, as life critical period sensitivity function. To this aim, testes from human at 6.5–10.5 gestational weeks (GW) or rat mouse comparable development...
The mechanisms regulating the entry into meiosis in mammalian germ cells remain incompletely understood. We investigated involvement of TGF-β family members fetal cell initiation. Nodal, a member family, and its target genes are precociously expressed embryonic gonads show sexual dimorphism favor developing testis. Nodal receptor genes, Acvr2a Acvr2b, Alk4, Tdgf1/Cripto, were identified male cells. itself, Tdgf1, Lefty1 Lefty2 targets signaling all found specifically To elucidate role this...
Transforming growth factors β1 and β2 (TGFβs) have recently been detected by immunohistochemistry in the fetal neonatal rat testis, aim of present study was to determine whether these can act as local regulators control number gonocytes. Testes were kept organ culture, TGFβ1 found dose-dependent inhibitory effect on gonocytes testes explanted day 13.5. Either or at 10 ng/ml reduced half after 2 days culture. TGFβs did not decrease BrdU labeling index Sertoli cells, whereas significantly...
Abstract Epidemiological, clinical, and experimental studies have suggested that excessive exposure to estrogens during fetal/neonatal life can lead reproductive disorders sperm abnormalities in adulthood. However, it is unknown whether endogenous concentrations of affect the establishment male fetal germ cell lineage. We addressed this question by studying testicular development mice which estrogen receptor (ER) β or ERα gene was inactivated. The homozygous inactivation ERβ (ERβ−/−)...
In human, the chronology of testicular development has been extensively studied, but factors implicated in onset and regulation gametogenesis steroidogenesis remain hardly known.To identify these factors, we developed an organ culture system for human fetal testes recovered during first trimester (6-12 wk) gestation. We aimed at investigating characteristics this by comparing vivo vitro steroidogenesis. Second, used to investigate effect on functions retinoic acid (RA), previously described...
In adulthood, the action of androgens on seminiferous tubules is essential for full quantitatively normal spermatogenesis and fertility. contrast, their role in fetal testis, particularly germ cell development, remains largely unknown. Using testicular feminized (Tfm) mice, we investigated effects a lack functional androgen receptor (AR) cells, also named gonocytes. We demonstrated that endogenous androgens/AR physiologically control gonocyte proliferation. observed an increase number...
Data from experiments conducted almost exclusively in the rat have established that some phthalates deleterious effects on fetal testis probably due to their antiandrogenic and/or estrogenic effects, but mechanisms of action remain unknown. A recent study reported also human with germ cell number, not steroidogenesis altered. Therefore, we used organ culture testes at different stages development analyze direct both and gonocyte determine if MEHP these functions can be extended other...
The mechanisms regulating germ line sex determination and meiosis initiation are poorly understood. Here, we provide evidence for the involvement of homeobox Msx transcription factors in foetal mammalian cells. Upon initiation, Msx1 Msx2 genes strongly expressed ovary, possibly stimulated by soluble found there: bone morphogenetic proteins Bmp2 Bmp4, retinoic acid. Analysis Msx1/Msx2 double mutant embryos revealed a majority undifferentiated cells remaining ovary and, importantly, decrease...