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DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis

Abstract : Many endocrine disruptors have been proven to impair the meiotic process that is mandatory to produce healthy gametes. Bisphenol A is emblematic as it impairs meiotic prophase I and causes oocyte aneuploidy following in utero exposure. However, the mechanisms underlying these deleterious effects remain poorly understood. Furthermore, the increasing uses of BPA analogs raise concerns for public health. Here, we investigated the effect on oogenesis in mouse of fetal exposure to two BPA analogs, Bisphenol A Diglycidyl Ether (BADGE) or Bisphenol AF (BPAF). These analogs delay meiosis initiation, increase MLH1 foci per cell and induce oocyte aneuploidy. We further demonstrate that these defects are accompanied by a deregulation of gene expression and aberrant mRNA splicing in fetal premeiotic germ cells. Interestingly, we observed an increase in DNA oxidation after exposure to BPA analogs. Specific induction of oxidative DNA damages during fetal germ cell differentiation causes similar defects during oogenesis, as observed in 8-Oxoguanine DNA Glycosylase (OGG1) deficient mice or after in utero exposure to potassium bromate (KBrO3), an inducer of oxidative DNA damages. Moreover, the supplementation of N-acetylcysteine (NAC) with BPA analogs counteracts the bisphenol-induced meiotic effect. Together our results position oxidative stress as a central event that negatively impacts the female meiosis with major consequences on oocyte quality. This could be a common mechanism of action for so called endocrine disruptors pollutants and it could lead to novel strategies for reprotoxic compounds.
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Preprints, Working Papers, ...
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Contributor : J. Pablo Radicella <>
Submitted on : Friday, April 2, 2021 - 12:11:00 PM
Last modification on : Friday, April 2, 2021 - 12:11:01 PM

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Sonia Abdallah, Delphine Moison, Margaux Wieckowski, Sébastien Messiaen, Emmanuelle Martini, et al.. DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis. 2021. ⟨cea-03188662⟩



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