Involvement of Bcl-2 family proteins in germ cell apoptosis during testicular development in the rat and pro-survival effect of stem cell factor on germ cells in vitro.
A large part of germ cells die apoptotically during testicular development in rodents. In the present study, a wave of germ cell apoptosis was observed between days 10 and 30 of postnatal life by in situ 3'-end labeling and DNA fragmentation analysis. To explore the potential involvement of Bcl-2 family members in this process, the expression and localization of some Bcl-2 family proteins (Bcl-2, Bcl-xL, Bcl-w, Bak, Bax, and Bad) and p53 were analyzed during testicular development in the rat by Western blotting and immunohistochemistry. The dynamic changes in the expression profiles of Bcl-2 family proteins are consistent with a model in which germ cells are primed for apoptosis during the first cycle of spermatogenesis by de novo expression of the death effectors Bax and Bad in a p53-dependent manner and these proteins are prevented from triggering further apoptosis after the first spermatogenic cycle has been set up by anti-apoptotic Bcl-2 family proteins Bcl-xL and Bcl-w. To examine whether the pro-survival effect of stem cell factor (SCF) on germ cells in vitro is mediated by Bcl-2 family proteins, the correlation between the pro-survival effect of SCF on germ cells and the expression of the above-mentioned apoptosis-related gene products in the seminiferous tubules at stage XII of the epithelial cycle were also investigated using a tubular culture system. The data suggest that SCF supports germ cell survival during spermatogenesis by up-regulating pro-survival Bcl-2 family proteins, Bcl-w and Bcl-xL, and down-regulating pro-apoptosis Bcl-2 family proteins, e.g. Bax.
Departments of Physiology and Pediatrics, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland.
W
W
Yan
J
J
Suominen
M
M
Samson
B
B
Jégou
J
J
Toppari
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000378:metabolism; D013093:Spermatogonia / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019089:Stem Cell Factor / Q000494:pharmacology*; D013737:Testis / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D019089:Stem Cell Factor; D016159:Tumor Suppressor Protein p53