Involvement of Fas system and active caspases in apoptotic signalling in testicular germ cells of ethanol-treated rats.
The Fas system is involved in the regulation of germ cell apoptosis associated with testicular injury in experimental animals exposed to various insults. We tested the hypothesis that enhanced germ cell apoptosis mediated by the up-regulation of the Fas system and the activation of caspases may be involved in ethanol-induced testicular injury. Adult Wistar rats were fed either ethanol in Lieber-DeCarli liquid diet or an isocaloric control diet for 12 weeks. Marked Sertoli cell vacuolization and germ cell degeneration were observed in the testes of ethanol-treated rats (ETR) by both light and electron microscopy. Enhanced apoptosis of germ cells in ETR was detected by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labelling (TUNEL) method, transmission electron microscopy, and was associated with elevated activity of caspase-3, -8 and -9. The expression levels of the Fas ligand (FasL) in Sertoli cells and of both Fas and caspase-3 in germ cells of ETR detected immunohistochemically were higher than those of the control testes. Furthermore, reverse transcriptase-polymerase chain reaction analysis demonstrated an increase in both Fas and FasL mRNA levels in ETR. Fas system up-regulation and the elevated activity of caspases in the testes of ETR may be a reflection of ethanol-induced testicular injury resulting in enhanced germ cells apoptosis, which may be involved in infertility associated with alcohol abuse.
Eid
Nabil A S
NA
Department of Anatomy and Biology, Osaka Medical College, Osaka, Japan.
Shibata
Masa-Aki
MA
Ito
Yuko
Y
Kusakabe
Ken
K
Hammad
Hanaa
H
Otsuki
Yoshinori
Y
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012671:Seminiferous Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor; D000431:Ethanol; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases