Autonomous Cell Death of Mouse Male Germ Cells during Fetal and Postnatal Period1

Germ cell degeneration is common in mammalian testes during the developmental as well as the adult period. To investigate the extent and mechanisms of male germ cell death during fetal and neonatal life, the testes of mice at various fetal and postnatal ages extending from 13 days of gestation to 7 wk after birth were examined by electron microscopy and/or terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Electron microscopy revealed that the number of cells with typical features of spermatogenic cell apoptosis was highest at 13 days of gestation, coinciding with the time of immigration of primordial germ cells into gonads. A second peak was observed around 10-13 days after birth when the first wave of spermatogenesis had started and active spermatogonial proliferation was present. Surprisingly, we found a significant number of dying cells around birth, which exhibited morphological features of necrotic death. In agreement with the results 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- to 13-day-old mice. To investigate the mechanisms of induction of germ cell death, we examined the expression of Fas antigen immunohistochemically using rabbit antiserum raised against synthetic peptides for part of mouse Fas antigen. We found that among various developmental stages investigated, positive immunostaining for Fas antigen was present between 17 days of gestation and 1 day after birth, with the most intensive staining occurring on 17 days of gestation. Therefore, Fas-induced pathways may be implicated in embryonic male germ cell death, not prepubertal spermatogenic cell death.