This work was supported by funding to PAF and CC from the Wellcome Trust (080388) and the European Community's Seventh Framework Programme under grant agreement no. 212885. (http://www.abdn.ac.uk/reef/). The authors would like to thank INRAE, SAAJ, experimental animal facility (Sciences de l'Animal et de l'Aliment de Jouy), especially Jean-Pierre Albert, Didier Mauchand, and Jean-François Alkombre.Peer reviewedPublisher PD

Cotinot, Corinne

Fowler , Paul A

Jouneau, Luc

Loup, Benoit

Mandon-Pepin, Beatrice

Poumerol, Elodie

Reproductive Toxicology

English

International audienceThe 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

Fowler, Paul

Mandon-Pepin, Béatrice

Hal-Diderot

BPA disrupts meiosis I in oogonia by acting on pathways including cell cycle regulation, meiosis initiation and spindle assembly

This work was supported by funding to PAF and CC from the Wellcome Trust (080388) and the European Community's Seventh Framework Programme under grant agreement no. 212885. (http://www.abdn.ac.uk/reef/). The authors would like to thank INRAE, SAAJ, experimental animal facility (Sciences de l'Animal et de l'Aliment de Jouy), especially Jean-Pierre Albert, Didier Mauchand, and Jean-François Alkombre.Peer reviewe

Aberdeen University Research

Fowler, Paul, A

Mandon-Pépin, Béatrice

HAL UVSQ

https://aura.abdn.ac.uk/bitstream/2164/19094/1/Loup_etal_RT_BPA_Disrupts_Meiosis_VOR.pdf

BPA disrupts meiosis I in oogonia by acting on pathways including cell cycle regulation, meiosis initiation and spindle assembly

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Hal-Diderot

Aberdeen University Research

HAL UVSQ