Do Prenatal Exposures Pose a Real Threat to Ovarian Function? BPA as a Case Study

Abstract

Fetal development represents a time of potential vulnerability due to rapid cell division, organ development and limited fetal kidney/liver activity for detoxification and metabolism of exposures. Health effects of prenatal toxicant exposure have previously been described, but there is little cohesive evidence surrounding effects on ovarian function. Using bisphenol A (BPA) as a case study, we seek to examine whether a prominent prenatal environmental exposure can pose a real threat to human ovarian function. To do so, we broadly review human oogenesis and menstrual cycle biology. We then present available literature addressing prenatal bisphenol A and diverse outcomes at the level of the ovary. We highlight relevant human cohorts and mammalian models to review the existing data on prenatal exposures and ovarian disruption. Doing so suggests that while current exposures to BPA have not shown marked or consistent results, there is data sufficient to raise concerns regarding ovarian function. Challenges in the examination of this question suggest the need for additional models and pathways by which to expand these examinations in humans.

Advances in human primordial follicle activation and premature ovarian insufficiency

“…Several animal studies have strongly linked BPA exposure to follicle depletion, and this effect is observed regardless of whether exposure occurs in utero, postnatally or during adulthood (reviewed in Richardson et al 2014). Consequently, some countries have implemented bans on BPA use based on these animal studies, as human data on the reproductive consequences of BPA remain scarce (Richardson et al 2014, Mathew & Mahalingaiah 2019. Coincidently, in a study of infertile women, those with higher than average urinary BPA were identified as having a decreased ovarian reserve, and another study explored IVF outcomes for women with higher serum BPA and observed lower pregnancy rates and higher association with miscarriage (Sugiura-Ogasawara et al 2005, Lamb et al 2008.…”

The ovarian follicle of ruminants: the path from conceptus to adult

“…For example, in pregnant ewes, the expression of fetal ovarian microRNAs is modified by exposure to BPA from Days 30 to 90 of gestation, leading to changes in developmental and functional insulin-related genes (Veiga-Lopez et al 2013). This observation builds on extensive literature suggesting that the prenatal fetal ovary is particularly sensitive to BPA, in both human and animal models, and that low BPA concentrations affect the epigenome of female germ cells in rodents (Eichenlaub-Ritter and Pacchierotti 2015; Chianese et al 2018;Mathew and Mahalingaiah 2019;Huang and Zeng 2021). The effects of environmental contaminants can also be transgenerational, although to date the most emphatic demonstration has been with rodent models.…”

Antimikrobiyal Peptitlere Yönelik Güncel Eğilimler; Nanotaşıyıcı Sistemeler ve Farmasötik Uygulamalar

“…Notably, this impact has been consistently found irrespective of the timing of exposure, whether it occurred during the prenatal period, postnatal period, or in adulthood (Richardson et al, 2014). As a result, numerous countries have enacted restrictions on the usage of BPA based on evidence derived from animal studies, given the inconclusive nature of available human data about the reproductive impacts of BPA (Richardson et al, 2014;Mathew & Mahalingaiah, 2019). A study conducted on women experiencing infertility revealed that individuals with urinary BPA levels exceeding the average demonstrated a diminished ovarian reserve.…”