Mitochondrial signaling pathway is also involved in bisphenol A induced germ cell apoptosis in testes.
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.
Wang
Qun
Q
Department of Toxicology, Anhui Medical University, Hefei, China.
Zhao
Xian-Feng
XF
Ji
Yan-Li
YL
Wang
Hua
H
Liu
Ping
P
Zhang
Cheng
C
Zhang
Ying
Y
Xu
De-Xiang
DX
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
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