IZUMI Shinichi Nagasaki University Graduate School of Biomedical Sciences, Department of Developmental and Reconstructive Medicine, Instructor, 大学院・医歯薬学総合研究科, 助手 (40264246)
SHIN Masashi Nagasaki University Graduate School of Biomedical Sciences, Department of Developmental and Reconstructive Medicine, Instructor, 大学院・医歯薬学総合研究科, 助手 (80145226)
HISHIKAWA Yoshitaka Nagasaki University Graduate School of Biomedical Sciences, Department of Developmental and Reconstructive Medicine, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (60304276)
In mammalian spermatogenesis, germ cell apoptosis is very common, though the molecular mechanism underlying the induction of apoptosis was largely unknown. In the present study, to gain molecular insights into the mechanism we examined the occurrence of germ cell apoptosis and the involvement of the Fas/ FasL and Bcl-2Bax systems in it in various damaged testis models with such as ischemia-reperfusion, cryptorchidism, endocrine disruptor treatment, anti-cancer drug treatment as well as normal neonatal and adult mouse testes. As a result, we found that the Fas expression is involved in the induction of germ cell apoptosis in the testes with ischemia-reperfusion and with a high dose (more than 1mg/KgBW) of estradiol-3-benzoate, diethylstilbestrol or bisphenol A. However, in the cases with a low dose (10-100ng/Kg BW) of these compounds and with experimental cryptorchidism, the number of TUNEL positive cells were affected by the expression of Bcl-2 and Bax and the cells were associated with cellular redistribution of Bax without any changes in the expression of Fas and FasL. In normal neonatal and adult testes, only Bax redistribution was correlated with TUNEL positive germ cells. Moreover, Bax redistribution was accompanied by the expression of cytochrome c and activated caspase 3. Collectively, in the normal and slightly damaged testes, Bax redistribution or mitochondrial pathway plays an essential role in the induction of germ cell death while the Fas system may be important in the case of heavily damaged testes. In addition, we showed that an intraperitoneal injection of anti-Fas antiserum, which blocks the interaction between Fas and Fast, inhibited the induction of germ cell apoptosis effectively, raising a possibility of manipulation of germ cell death. Finally, the analysis of mitochondrial pathway in the induction of germ cell apoptosis would be required in the near future.