Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the Fas-mediated pathway

The life cycle of many cell types can hinge on the presence of death factor s that can control programmed cell death. The Fas-mediated apoptotic pathwa y has been implicated in controlling apoptosis during spermatogenesis in a number of mammalian species. In the human, the presence of nuclear DNA dama ge in ejaculated spermatozoa has pointed to a possible role for apoptosis d uring spermatogenesis. The presence of other molecular markers of apoptosis has, however, not been shown. More importantly, differences in these marke rs have not been investigated in men with normal and abnormal sperm paramet ers. In this study we examine for the presence of the cell surface protein Fas in ejaculated human spermatozoa. Ejaculated spermatozoa (55 samples) we re labeled with anti-human Fas antibody and the number of spermatozoa displ aying Fas were counted using a fluorescence-activated cell sorter (FACS). I n 30/31 (96.8%) normal males (>20 million sperm per milliliter), less than 10% of the spermatozoa were Fas positive. In contrast, 14/24 (58.3%) oligoz oospermic samples (<20 million sperm per milliliter) contained more than 10 % Fas-positive spermatozoa. Similar differences were observed in men whose spermatozoa had poor motility and morphology. These results indicate that a poptosis is a major mechanism in regulating spermatogenesis in the human an d that there are clear differences in molecular markers of apoptosis betwee n males with normal and abnormal sperm parameters. We propose that the pres ence of Fas-labeled spermatozoa in the ejaculate of these men is indicative of an "abortive apoptosis" having taken place, whereby the normal apoptoti c mechanisms have misfunctioned, have been overridden, or have not been com pleted. (C) 1999 Academic Press.