Mechanisms of reproductive toxicity and endocrine disruption of bisphenols and per- and polyfluoroalkyl substances (PFAS): Implications for women's reproductive health

Bisphenols and per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental endocrine-disrupting chemicals with widespread human exposure and growing concern regarding their reproductive toxicity. This review integrates current experimental and epidemiologic evidence to evaluate the potential endocrine-disrupting mechanisms and reproductive toxicity of bisphenols, particularly bisphenol A (BPA), and PFAS on female reproductive health. Available data demonstrate that these chemicals disrupt key hormonal and cellular processes regulating female reproduction, including hypothalamic-pituitary-ovarian axis signaling, ovarian steroidogenesis and folliculogenesis, oocyte quality and maturation, uterine structure and function, and oxidative stress. Across in vitro and animal models, BPA and PFAS consistently induce hormonal dysregulation, oxidative stress, mitochondrial dysfunction, and epigenetic alterations that impair coordinated ovarian-uterine signaling. Importantly, these mechanistic findings align with epidemiologic studies reporting associations between BPA and PFAS exposure and increased risk of adverse reproductive outcomes, including endometriosis, polycystic ovary syndrome, diminished ovarian reserve, premature ovarian insufficiency, infertility, and adverse pregnancy outcomes. Collectively, this review underscores the relevance of environmental chemical exposure as a modifiable risk factor for female reproductive health and emphasizes the need for further integration of mechanistic and population-based research to inform exposure assessment, risk evaluation, and regulatory strategies to reduce exposure to endocrine-disrupting chemicals and protect female reproductive health.