Sensitivity of testicular germ cells to toxicant-induced apoptosis in gld mice that express a nonfunctional form of Fas ligand.
Germ cell apoptosis in testis is essential for functional spermatogenesis. Recent evidence suggests that the Fas signaling system is critical for the regulation of testicular germ cell apoptosis. To further evaluate the Fas signaling system in testis, we examined the incidence of germ cell apoptosis in gld mice that lack a functional Fas-signaling pathway. gld mice have a small, but significant, increase in testis weight and numbers of spermatid heads per testis compared with wild-type mice. In addition, gld mice have a small increase in the spontaneous incidence of germ cell apoptosis, as indicated by characteristic DNA fragmentation via the terminal deoxynucleotidyl-transferase-mediated deoxy-UTP nick end labeling assay. To test the role of the Fas system in toxicant-induced germ cell apoptosis, mice were exposed to either a Sertoli cell- or germ cell-specific toxicant [mono-(2-ethylhexyl)phthalate (MEHP; 1 g/kg) or 5 Gy radiation, respectively]. These two exposure paradigms induced extensive increases in germ cell apoptosis in wild-type mice. However, exposure of gld mice to MEHP caused only a minimal increase in germ cell apoptosis, whereas they were as sensitive as wild-type mice to radiation exposure. These data indicate that the Fas signaling pathway is 1) involved in regulating the numbers of germ cells in the testis, 2) crucial for the initiation of germ cell apoptosis after MEHP-induced Sertoli cell injury, and 3) differentially active in the cell-specific regulation of germ cell apoptosis that occurs as a consequence of Sertoli cell vs. germ cell injury.
Richburg
J H
JH
Division of Pharmacology and Toxicology, University of Texas College of Pharmacy, Austin 78712-1074, USA. john_richburg@mail.utexas.edu
Nañez
A
A
Williams
L R
LR
Embree
M E
ME
Boekelheide
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D053938:DNA Fragmentation; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D053222:Fas Ligand Protein; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012016:Reference Values; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D013737:Testis / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D014965:X-Rays
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate