Exposure to bisphenol A at physiological concentrations observed in Chinese children promotes primordial follicle growth through the PI3K/Akt pathway in an ovarian culture system

• Published in: Toxicology in vitro 2014-12, Vol.28 (8), p.1424-1429
• Main Authors: Zhao, Qian, Ma, Yan, Sun, Ning-xia, Ye, Chen, Zhang, Qing, Sun, Shu-han, Xu, Chen, Wang, Fang, Li, Wen
• Format: Article
• Language: English
• Subjects: Animals; Benzhydryl Compounds - toxicity; Bisphenol A; Child; Female; Humans; Male; Mice; Mice, Inbred C57BL; Organ Culture Techniques; Ovarian Follicle - drug effects; Ovarian Follicle - growth & development; Over-activation; Phenols - toxicity; Phosphatidylinositol 3-Kinases - physiology; PI3K/Akt pathway; Primordial follicle pool; Proto-Oncogene Proteins c-akt - physiology; Signal Transduction - drug effects
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2014.07.009

•Exposure to BPA promotes primordial follicle over-activation.•The dose similar to that observed in children promotes follicle activation.•BPA reduces the number of follicle atresia.•PI3K/Akt pathway may be involved in the BPA-mediated follicle activation. The worldwide increase in the use of bisphenol A (BPA) has resulted in increased human exposure, which could affect human reproductive function. Few studies have investigated the effect of BPA exposure on the primordial follicle pool. In this study, we employed a neonatal ovarian culture system comprising organ obtained from female C57BL/6 pups on postnatal day 4 to assess the effect of BPA on the primordial follicle pool. Ovaries were cultured with BPA (0.1μM, physiological concentration found in children’s blood, and 1μM, 10μM) or vehicle for 10days. Our study revealed that the primary follicle number increased during the early time points (⩽5days), and we observed a reduction in the primordial follicle pool at a later time point (day 10). This reduction at day 10 was due to increased follicle activation and reduced follicle atresia, as determined by immunohistochemistry for Ki-67 and active caspase-3. Then we examined the phosphatidylinositol-3-kinase (PI3K)/Akt pathway, which is known to be important for early follicle growth. BPA exposure induced the upregulation of the PI3K/Akt pathway, which was reversed by concomitant treatment with PI3K inhibitor. Our results reveal a novel mechanism for BPA-induced primordial follicle activation that involves the PI3K/Akt pathway.