AUTONOMOUS CELL-DEATH OF MOUSE MALE GERM-CELLS DURING FETAL AND POSTNATAL-PERIOD

Germ cell degeneration is common in mammalian testes during the develo pmental as well as the adult period. To investigate the extent and mec hanisms of male germ cell death during fetal and neonatal life, the te stes of mice at various fetal and postnatal ages extending from 13 day s of gestation to 7 wk after birth were examined by electron microscop y and/or terminal deoxynucleotidyl transferase-mediated dUTP nick end- labeling (TUNEL). Electron microscopy revealed that the number of cell s with typical features of spermatogenic cell apoptosis was highest at 13 days of gestation, coinciding with the time of immigration of prim ordial germ cells into gonads. A second peak was observed around 10-13 days after birth when the first wave of spermatogenesis had started a nd active spermatogonial proliferation was present. Surprisingly, we f ound a significant number of dying cells around birth, which exhibited morphological features of necrotic death. In agreement with the resul ts of electron microscopy, TUNEL staining revealed that the dying germ cells present around birth were TUNEL negative, while positive nuclei were abundant in the lumen of seminiferous tubules of testes of 10- t o 13-day-old mice. To investigate the mechanisms of induction of germ cell death, we examined the expression of Fas antigen immunohistochemi cally using rabbit antiserum raised against synthetic peptides for par t of mouse Fas antigen. We found that among various developmental stag es investigated, positive immunostaining for Fas antigen was present b etween 17 days of gestation and 1 day after birth, with the most inten sive staining occurring on 17 days of gestation. Therefore, Fas-induce d pathways may be implicated in embryonic male germ cell death, not pr epubertal spermatogenic cell death.