title: Mitochondrial signaling pathway is also involved in bisphenol A induced germ cell apoptosis in testes.
abstract: Bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. An earlier study showed that BPA-induced germ cell apoptosis through the Fas/FasL apoptotic pathway. In the present study, we aimed to investigate whether the mitochondrial pathway is also involved in the process of BPA-mediated germ cell apoptosis in testes. Male mice were administered with BPA (160 or 480 mg/kg) by gavage daily from postnatal day 35 (PND35) to PND49. Germ cell apoptosis in testes was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). As expected, the number of TUNEL+ germ cells per tubule and the percentage of tubules with TUNEL+ germ cells were significantly increased in testes of mice treated with BPA during puberty. TUNEL+ germ cells were observed mainly in stages VII-VIII seminiferous tubules in testes. An increase in the level of Fas and FasL was observed in testes of mice exposed to BPA during puberty. In addition, pubertal BPA exposure evoked the activation of caspase-8 and caspase-3 in testes. Interestingly, pubertal BPA exposure also caused the translocation of cytochrome c from mitochondria into cytosol. In addition, pubertal BPA exposure upregulated the level of Bax and active caspase-9 in testes. Taken together, these results suggest that pubertal BPA exposure induces germ cell apoptosis in testes through not only the Fas/FasL signaling pathway but also the mitochondrial apoptotic pathway.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Zhao
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Ji
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds; D045304:Cytochromes c / Q000032:analysis; D053222:Fas Ligand Protein / Q000032:analysis; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D019014:fas Receptor / Q000032:analysis; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D045304:Cytochromes c; D053222:Fas Ligand Protein; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; C006780:bisphenol A; D000098826:Bisphenol A Compounds