Germ cell-specific decrease of acrosomal proteolytic activity, sperm motility, and number in mitomycin C-treated mice

Abstract

Assessment of mammalian sperm acrosomal proteolytic activity, sperm motility, and sperm count may be useful for detecting mutagens, carcinogens, developmentally active agents, and antifertility effects. Groups of six albino mice were given a single i.p. injection of 5 mg/kg mitomycin C (MC) or saline. One treated and one control group of mice were killed 1, 3, 5, 7, or 10 weeks later. Sperm extracted from the vasa deferentia at these killing times were derived from cells treated as spermatozoa, spermatids, preleptotene-late spermatogonial cells, spermatogonial cells, and spermatogonial stem cells. In sperm derived from treated preleptotene or spermatogonial cells, the sperm count, sperm motility, and acrosomal proteolytic activity were decreased significantly. Acrosomal proteolytic activity was also decreased in sperm from spermatogonial stem cells. None of these sperm phenotypes were decreased in treated spermatozoa and spermatids. We propose the hypothesis that induced loss of sperm motility and acrosomal proteolytic activity in single spermatozoa derived from MC-treated spermatogonial cells is caused by mutational or developmental effects, whereas in preleptotene-derived and late-spermatogonium-derived sperm similar dysfunction results from developmental effects. Our data support the hypothesis indirectly. Since a low sperm count is correlated with decreased fertility and acrosomal proteolytic activity is essential for penetration of the zona pellucida by the sperm, the presence of these sperm phenotypes may help to detect chemicals with antifertility effects.

Use of Sperm Enzymes to Detect Genotoxic Agents.

“…As a supplement to the sperm head shape abnormality test, several "4 -investigators have suggested the use of histochemical assays to examine the function of enzymes in single sperm after chemical treatment (Burkhart et al, 1982;Ginsberg et al, 1982;Ficsor et al, 1983). The sperm enzyme tests (SET) have been successful in detecting chemically-induced dysfunction in sperm which had normal head shapes (Ficsor et al,198 4 a).…”