Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand.
It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT) mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times. After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITC-conjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.
Hu
Jia Hua
JH
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Jiang
Jie
J
Ma
Ying Hua
YH
Yang
Na
N
Zhang
Mao Hu
MH
Wu
Min
M
Fei
Jian
J
Guo
Li He
LH
D000818:Animals; D017209:Apoptosis; D000431:Ethanol / Q000633:toxicity*; D053222:Fas Ligand Protein; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012671:Seminiferous Tubules / Q000187:drug effects / Q000648:ultrastructure; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D000431:Ethanol