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In utero germ-cell exposure to bisphenols: a role for oxidative damage in oocyte aneuploidy

In a work published in Environmental Pollution, researchers from iRCM's LDG laboratory explored the effects of exposure to two bisphenol A substitutes, BADGE and BPAF, on murine germ cells, and more specifically on oocytes and their precursors. Their results show that oxidative damage caused by the substitutes has important consequences on oocyte quality.

Published on 17 January 2023

Over the past few decades, the medical community has observed a significant rise in female reproductive disorders, for which exposure to the numerous pollutants present in the environment appears to be a common denominator. Bisphenol A (BPA), a compound widely used in plastics manufacturing, stands out among those pollutants. It was the first to be shown to alter oogenesis and lead to the formation of oocytes with an abnormal number of chromosomes (aneuploidy), in turn responsible for numerous miscarriages and fertility disorders. Although the mechanisms driving its deleteriousness remain mysterious, these observations have led to BPA use restrictions in many countries. However, those restrictions have led to the use of BPA substitutes—for which possible oocyte-toxic effects have not yet been characterized.

Aiming to bring light to the subject  the researchers at the Laboratory of Development of the Gonads (LDG; iRCM) decided to evaluate bisphenol A diglycidyl ether (BADGE) and bisphenol AF (BPAF). Both are used as bisphenol A substitutes but may present reproductive health worries of their own. In its study performed in a mouse model and published in Environmental Pollution, the team showed that fetal exposure to environmental concentrations of BADGE or BPAF caused oocyte defects in mature mice comparable to those provoked by fetal BPA exposure.

Via genetic and chemical models, the team was able to propose that the deleterious effects of bisphenols on mature oocytes results from their ability to induce oxidative lesions on DNA at a key step in germinal cell differentiation during the fetal period. Such lesions may alter the initiation of meiosis, that is, the process resulting in the production of the female (ovum) and male (spermatozoon) gametes. These disturbances may lead ultimately to errors in chromosome segregation during the metaphase of meiosis, and that faulty segregation to oocyte aneuploidy.

This study by the LDG team shows that not only BPA but also its substitutes can alter oocyte quality, as may numerous other oxidizing pollutants.

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