Prenatal bisphenol a exposure leads to reproductive hazards on male offspring via the Akt/mTOR and mitochondrial apoptosis pathways

Background: Bisphenol A (BPA) exposure is ubiquitous, and in laboratory animals and humans, exposure has been associated with male spermatogenesis dysfunction. However, it is largely unknown if this association has a fetal origin. Objective: The aim of this research is to explore the mechanism whereby prenatal BPA exposure exerts its reproductive toxicities on spermatogenesis in male offspring. Methods: We fed pregnant SD rats BPA at doses ranging from 1 to 100 mg/kg body weight during gestation days 14-21. The male offspring were euthanized at postnatal day 21, and the levels of sex hormones and reactive oxygen species (ROS), expressions of proteins and genes in the Akt/mTOR, and mitochondrial apoptosis pathways were detected. Several closely linked autophagy indexes were also measured incidentally. Additionally, semen quality of adult offspring was tested at the end of the study. Results: The results revealed that prenatal BPA exposure can cause endocrine disruption and oxidative stress in male offspring, leading to inhibition of spermatogenesis by suppressing the Akt/mTOR pathway and activating the mitochondrial apoptosis pathway. Conclusions: These preliminary results indicate noteworthy and far-reaching effects of BPA on the reproductive system of male offspring. (C) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1007-1023, 2017.