Effects of gestational and lactational bisphenol AF exposure on female offspring reproductive function during two developmental stages

Bisphenol AF (BPAF), a widely used substitute for bisphenol A (BPA), has been widely detected in pregnant women, raising concerns about its potential effects on reproductive health. However, studies on the reproductive toxicity of BPAF in mammals remain limited. This study aimed to investigate the reproductive toxicity and underlying mechanisms of BPAF exposure during gestation and lactation. Pregnant Sprague-Dawley rats were randomly assigned to four groups (n = 10/group) and administered BPAF by oral gavage (0, 2, 10, or 50 mg/kg/d in corn oil) from gestational day (GD) 0 to postnatal day (PND) 21. Female offspring [first filial generation (F1)] were examined at PND21 and PND70 for reproductive outcomes and steroidogenic alterations. Gestational and lactational BPAF exposure significantly reduced anogenital distance (AGD) at PND21, from 12.05 ± 0.59 mm in controls to 11.54 ± 0.50 mm in the 50 mg/kg group (P < 0.001). At PND21, serum estradiol (E2) levels were decreased in the 2 and 10 mg/kg BPAF groups compared with controls (P < 0.05). By PND70, all BPAF-exposed offspring showed reduced E2 and testosterone (T) levels (P < 0.05). In addition, BPAF exposure increased follicular atresia and downregulated the mRNA expression of key steroidogenic genes (StAR, CYP11A1, 17β-HSD, and CYP19A1; P < 0.05) at PND70. Our findings indicate that BPAF exposure during gestation and lactation impairs reproductive function in F1 females and may exert long-term effects through disruption of ovarian steroidogenesis. Further research is warranted to confirm these outcomes.