Impact of Bisphenol A and its alternatives on oocyte health: a scoping review

BACKGROUND Bisphenol A (BPA) is an endocrine disrupting chemical released from plastic materials, including food packaging and dental sealants, persisting in the environment and ubiquitously contaminating ecosystems and human populations. BPA can elicit an array of damaging health effects and, alarmingly, ‘BPA-free’ alternatives mirror these harmful effects. Bisphenol exposure can negatively impact female fertility, damaging both the ovary and oocytes therein. Such damage can diminish reproductive capacity, pregnancy success, and offspring health. Despite global government regulations in place to indicate ‘safe’ BPA exposure levels, these policies have not considered the effects of bisphenols on oocyte health. OBJECTIVE AND RATIONALE This scoping review was conducted to evaluate evidence on the effects of BPA and BPA alternatives on standardized parameters of oocyte health. In doing so, this review addresses a critical gap in the literature providing a comprehensive, up-to-date synthesis of the effects of bisphenols on oocyte health. SEARCH METHODS This scoping review was conducted in accordance with PRISMA guidelines. Four databases, Medline, Embase, Scopus, and Web of Science, were searched twice (23 February 2022 and 1 August 2023) to capture studies assessing mammalian oocyte health post-bisphenol exposure. Search terms regarding oocytes, ovarian follicles, and bisphenols were utilized to identify relevant studies. Manuscripts written in English and reporting the effect of any bisphenol on mammalian oocyte health from all years were included. Parameters for toxicological studies were evaluated, including the number of bisphenol concentrations/doses tested, dosing regimen, biological replicates and/or animal numbers, and statistical information (for human studies). Standardized parameters of oocyte health including follicle counts, oocyte yield, oocyte meiotic capacity, morphology of oocyte and cumulus cells, and oocyte meiotic spindle integrity were extracted across the studies. OUTCOMES After screening 3147 studies, 107 studies of either humans or mammalian animal models or humans were included. Of the in vitro exposure studies, 96.3% (26/27) and 94.1% (16/17) found at least one adverse effect on oocyte health using BPA or BPA alternatives (including BHPF, BPAF, BPB, BPF, and BPS), respectively. These included increased meiotic cell cycle arrest, altered morphology, and abnormal meiotic spindle/chromosomal alignment. In vivo, 85.7% (30/35) of studies on BPA and 92.3% (12/13) on BPA alternatives documented adverse effects on follicle development, morphology, or spindle/chromosome alignment. Importantly, these effects were recorded using levels below those deemed ‘safe’ for human exposure. Over half (11/21) of all human observational studies showed associations between higher urinary BPA levels and reduced antral follicle counts or oocyte yield in IVF patients. Recommendations are presented based on the identified shortcomings of the current evidence, incorporating elements of FDA requirements for future research in the field. WIDER IMPLICATIONS These data highlight the detrimental impacts of low-level BPA and BPA alternative exposure, contributing to poor oocyte quality and reduced fertility. These outcomes are valuable in promoting the revision of current policies and guidelines pertaining to BPA exposure internationally. This study serves as a valuable resource to scientists, providing key recommendations on study design, reporting elements, and endpoint measures to strengthen future studies. Ultimately, this review highlights oocyte health as a fundamentally important endpoint in reproductive toxicological studies, indicating an important direction for future research into endocrine disrupting chemicals to improve fertility outcomes.