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 s ignaling 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 ind icated by characteristic DNA fragmentation via the terminal deoxxynucleotid yl-transferase-mediated deoxy-UTP nick end labeling assay. To test the role of the Fas system in toxicant-induced germ cell apoptosis, mice were expos ed to either a Sertoli cell- or germ cell-specific toxicant [mono-(2-ethylh exyl)phthalate (MEHP; 1 g/kg) or 5 Gy radiation, respectively]. These two e xposure paradigms induced extensive increases in germ cell apoptosis in wil d-type mice. However, exposure of gld mice to MEHP caused only a minimal in crease in germ cell apoptosis, whereas they were as sensitive as wild-type mice to radiation exposure. These data indicate that the Fas signaling path way 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 Sert oli cell injury, and 3) differentially active in the cell-specific regulati on of germ cell apoptosis that occurs as a consequence of Sertoli cell us. germ cell injury.