title: 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.
abstract: 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 (0.1 μM, physiological concentration found in children's blood, and 1 μM, 10 μM) or vehicle for 10 days. Our study revealed that the primary follicle number increased during the early time points (⩽5 days), 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.
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ning-Xia
authors.initials: NX
authors.lastname: Sun
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ye
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, China. Electronic address: wfsjz@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Reproductive Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: liwenlyy@sina.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development; D010636:Phenols / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Over-activation; PI3K/Akt pathway; Primordial follicle pool