BPA disrupts meiosis I in oogonia by acting on pathways including cell cycle regulation, meiosis initiation and spindle assembly
| Autor: | Benoit Loup, Elodie Poumerol, Luc Jouneau, Paul A. Fowler, Corinne Cotinot, Béatrice Mandon-Pépin |
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| Přispěvatelé: | Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Aberdeen, European Project: 212885,EC:FP7:ENV,FP7-ENV-2007-1,REEF(2008), European Project: 080388,WT::(2006) |
| Rok vydání: | 2022 |
| Předmět: |
cumulus-oocyte complex
Meiosis I Stimulated by Retinoic acid gene 8 COC Toxicology spindle assembly checkpoint Organ culture retinoic acid receptor agonist Oogonia Fetal ovary Organ culture Meiosis Oogonia BPA Sheep RA Bisphenol A Phenols Retinoic acid Animals Humans STRA8 Benzhydryl Compounds [SDV.BDD]Life Sciences [q-bio]/Development Biology Sheep Fetal ovary days post coitum PGC SAC DPC BPA Meiosis primordial germ cell Oocytes Female AM580 |
| Zdroj: | Reproductive Toxicology Reproductive Toxicology, 2022, 111, p. 166-177. ⟨10.1016/j.reprotox.2022.06.001⟩ |
| ISSN: | 0890-6238 |
| Popis: | International audience; The negative in utero effects of bisphenol A (BPA) on female reproduction are of concern since the ovarian reserve of primordial follicles is constituted during the fetal period. This time-window is difficult to access, particularly in humans. Animal models and explant culture systems are, therefore, vital tools for investigating EDC impacts on primordial germ cells (PGCs). Here, we investigated the effects of BPA on prophase I meiosis in the fetal sheep ovary. We established an in vitro model of early gametogenesis through retinoic acid (RA)-induced differentiation of sheep PGCs that progressed through meiosis. Using this system, we demonstrated that BPA (3 ×10-7 M & 3 ×10-5 M) exposure for 20 days disrupted meiotic initiation and completion in sheep oogonia and induced transcriptomic modifications of exposed explants. After exposure to the lowest concentrations of BPA (3 ×10-7 M), only 2 probes were significantly up-regulated corresponding to NR2F1 and TMEM167A transcripts. In contrast, after exposure to 3 × 10-5 M BPA, 446 probes were deregulated, 225 were down- and 221 were up-regulated following microarray analysis. Gene Ontology (GO) annotations of differentially expressed genes revealed that pathways mainly affected were involved in cell-cycle phase transition, meiosis and spindle assembly. Differences in key gene expression within each pathway were validated by qRT-PCR. This study provides a novel model for direct examination of the molecular pathways of environmental toxicants on early female gametogenesis and novel insights into the mechanisms by which BPA affects meiosis I. BPA exposure could thereby disrupt ovarian reserve formation by inhibiting meiotic progression of oocytes I and consequently by increasing atresia of primordial follicles containing defective oocytes. |
| Databáze: | OpenAIRE |
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