Benzophenone-3 (BP3), bisphenol A (BPA), and their combination impair ovarian response to gonadotropin stimulation in a multi-exposure multiparity model

Despite prevailing evidence that endocrine-disrupting chemicals (EDCs) may exert effects across multiple pregnancies, most studies focus on the first pregnancy Using a multiparity murine model, we evaluated the effects of benzophenone-3 (BP3), bisphenol-A (BPA) or the combination (BP3 +BPA) exposure over two gestational periods (P1 and P2) on pregnancy outcomes and the gonadal function in female offspring from each pregnancy. While maternal weight, litter size, and sex ratio were unaffected, gestation length was altered in BPA and BP3 +BPA groups both in P1 and P2. Ovulation was affected in P2 offspring in all EDC exposed groups. Notably, antral follicle numbers were reduced in all exposed groups, while BPA and BP3 +BPA exposure diminished the primordial follicle reserve in P2 offspring. Estradiol levels were elevated in P2 offspring in the BP3 +BPA group with hCG stimulation. These findings highlight the importance of considering cumulative exposure and exposure to combinations of BP3 and BPA when assessing the long-term reproductive effects of EDCs.