SPONTANEOUS GERM-CELL APOPTOSIS IN HUMANS - EVIDENCE FOR ETHNIC-DIFFERENCES IN THE SUSCEPTIBILITY OF GERM-CELLS TO PROGRAMMED CELL-DEATH

Spontaneous death of certain classes of germ cells has been shown to b e a constant feature of normal spermatogenesis in a variety of mammali an species, including the human. Recent studies on various animal mode ls have demonstrated that apoptosis is the underlying mechanism of ger m cell death during normal spermatogenesis. Withdrawal of gonadotropin s and/or testosterone further accelerates the germ cell apoptosis. We examined the involvement of apoptosis in the spontaneous loss of germ cells in men. Testicular samples obtained at autopsy from 5 Chinese an d 9 non-Hispanic Caucasian men were analyzed. To identify individual g erm cells undergoing apoptosis, me used a modified terminal deoxynucle otidyl transferase-mediated deoxy-UTP nick end labeling technique that detects germ cell apoptosis with high sensitivity and specificity. Te sticular sections from all 14 subjects exhibited spontaneous occurrenc e of germ cell apoptosis involving spermatogonia, spermatocytes, and s permatids (apoptotic indexes, 1.6 +/- 0.4, 2.8 +/- 0.6, and 5.5 +/- 1. 2, respectively). The incidence of spermatogonial (2.8 +/- 0.8 vs. 1.0 +/- 0.2) as well as spermatid (9.3 +/- 2.1 vs. 3.4 +/- 0.9) apoptosis was higher in Chinese than in Caucasian men. A higher incidence of sp ermatocyte apoptosis was also noted for Chinese (4.4 +/- 1.4) compared to Caucasian (1.9 +/- 0.4) men, but the difference was not statistica lly significant. These results suggest that germ cell death during nor mal spermatogenesis in men occurs via apoptosis and provide evidence f or ethnic differences in the inherent susceptibility of germ cells to programmed cell death. Our data may also help to explain the greater e fficacy of testosterone-induced spermatogenic suppression to azoosperm ia observed in Asian compared to non-Asian men.