In utero exposure to bisphenol A disrupts fetal testis development in rats

Bisphenol A (BPA) is widely used in consumer products and is a potential endocrine disruptor linked with abnormal development of male reproductive tract. However, its action and its effects on the pathways in the development of male gonad are still unclear. Here we report that effects of BPA exposure during gestation on male gonad development. Sprague-Dawley rats were gavaged daily with BPA (0, 4, 40, and 400 mg/kg body weight) from gestational day 12 to day 21. BPA dose-dependently decreased serum testosterone levels (0.45 ± 0.08 ng/ml and 0.32 ± 0.08 ng/ml for 40 and 400 mg/kg BPA, respectively) versus the control level (1.11 ± 0.22 ng/ml, Mean ± SE). BPA lowered Leydig cell Insl3 and Hsd17b3 mRNA and their protein levels at doses of 40 and 400 mg/kg. BPA also lowered Leydig cell (Lhcgr, Cyp11a1, and Cyp17a1) and Sertoli cell (Amh) mRNA and their protein levels at 400 mg/kg. BPA decreased fetal Leydig cell number via inhibiting their proliferation, but it did not affect fetal Sertoli cell number. In conclusion, the current study shows that in utero exposure to BPA inhibits fetal Leydig and Sertoli cell differentiation, possibly disrupting the development of male reproductive tract.