Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice

Endocrine disrupting chemicals (EDCs), like bisphenol A (BPA) and benzophenone-3 (BP-3), can interfere with hormone systems, posing risks to fertility and reproduction. Exposure to EDCs is unavoidable making it a relevant environmental health topic, however the impact of real-life EDC mixtures is largely unknown. This study explored the effects of a combined BPA and BP-3 exposure at tolerable intake levels for humans during pregnancy and early life on ovarian development and function in an established mouse model. Mice were daily exposed to concentrations of 4 µg/kg BPA orally, 50 mg/kg BP-3 dermally, and the combination of BPA+BP-3 through gestation and lactation, a susceptible developmental period. Female offspring of BPA and BP-3 exposed mice exhibited increased birth weight and elevated bodyweight by postnatal day 7. By day 30, after hormonal stimulation to induce ovulation, exposed offspring showed disrupted ovarian follicle maturation and altered ovarian response to stimulation with exogenous gonadotropins. Moreover, the number of NK cells rose in the ovaries, and genes linked to hormone signaling, hormone synthesis, and ovarian tissue remodeling were altered relative to unexposed controls. These findings suggest that early life exposure to BPA and BP-3 at environmentally relevant doses impairs ovarian development and function in mice indicating that immune cells and hormonal signaling in the ovaries are targets of endocrine disruptors at relevant concentrations. Such endocrine disruption may be compromising fertility and reproductive health in later life. Our research underscores the importance of investigating the impact of combined EDC exposure on the reproductive system.