Foetal exposure to the bisphenols BADGE and BPAF impairs meiosis through DNA oxidation in mouse ovaries. (15th January 2023)

• Record Type: Journal Article
• Authors: Abdallah, Sonia; Jampy, Amandine; Moison, Delphine; Wieckowski, Margaux; Messiaen, Sébastien; Martini, Emmanuelle; Campalans, Anna; Radicella, Juan Pablo; Rouiller-Fabre, Virginie; Livera, Gabriel; Guerquin, Marie-Justine
• Is Part Of: Environmental pollution. Volume 317(2023)
• Publication Date: 2023-01-15
• Subjects: bisphenols -- Meiosis -- DNA oxidation -- Environmental pollutant -- Epigenetic -- Oogenesis; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.120791
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Many endocrine disruptors have been proven to impair the meiotic process which is required for the production of healthy gametes. Bisphenol A is emblematic of such disruptors, 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 use of BPA alternatives raises concerns for public health. Here, we investigated the effects of foetal exposure to two BPA alternatives, bisphenol A Diglycidyl Ether (BADGE) and bisphenol AF (BPAF), on oogenesis in mice. These compounds delay meiosis initiation, increase the number of MLH1 foci per cell and induce oocyte aneuploidy. We further demonstrate that these defects are accompanied by changes in gene expression in foetal premeiotic germ cells and aberrant mRNA splicing of meiotic genes. We observed an increase in DNA oxidation after exposure to BPA alternatives. Specific induction of oxidative DNA damage during foetal 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 damage. The supplementation of BPA alternatives with N-acetylcysteine (NAC) counteracts the effects of bisphenols on meiosis. Together, our results propose oxidative DNA lesion as an event that negatively impacts female meiosis with major consequences on oocyte quality. This could be a common mechanism of action for numerous environmental pro-oxidant pollutants, and its discovery, could lead to reconsider the adverse effect of bisphenol mixtures that are simultaneously present in our environment. Graphical abstract: Image 1 Highlights: BPAF and BADGE induce similar defects to those triggered by BPA in fetal murine ovary. Disruptions during transcriptional meiotic program set-up may cause these defects. DNA methylation erasure before meiosis initiation was impaired by bisphenols. BPAF and BADGE induce oxidative DNA lesions in fetal germ cells before meiosis. Elevation of oxidative DNA lesions lead to meiotic disruption and aneuploidy.