Maternal exposure to bisphenol A during pregnancy interferes testis development of F1 male mice

摘要

This study was conducted to investigate the effects of maternal exposure to bisphenol A (BPA) on testis development of F1 male mice. The BPA exposure model of pregnant mice was prepared by intragastric administration of BPA at the doses of 0, 2.5, 5, 10, 20, and 40mg/kg/day at gestation day (GD) 0.5-17.5. The testis index of the offspring mice was calculated at postnatal day (PND) 21 and PND 56. The results showed that maternal exposure to 20mg/kg BPA during pregnancy significantly increased the testicular index of F1 males at PND 21, and 40mg/kg BPA significantly decreased the testicular index of F1 males at PND 56 (P<0.01). BPA significantly reduced serum testosterone (T) and estradiol (E-2) levels, and improved testicular ER alpha and ER beta levels in F1 males at both PND 21 and PND 56. BPA exposure also upregulated transcription of testicular Dnmt1 and inhibited the transcription of testicular Dnmt3A and Dnmt3B in F1 mice at PND 21. BPA reduced the transcriptional level of testicular DNA methyltransferase (Dnmt), increased the expression of testicular caspase-7, caspase-9, and bax, and decreased the expression of bcl-2 in F1 mice at PND 56. Consistent with that, BPA improved the apoptosis rate in the testis at PND 56 (P<0.01 or P<0.05). Our study indicates that BPA disrupts the secretion of testosterone, estradiol, and estrogen receptors by interfering with the transcription of testicular DNA methyltransferase (Dnmt) in offspring males, which damages testicular tissues and affects the potential reproductive function.