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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.
Insights
Mitomycin C exposure significantly reduced sperm count, motility, and acrosomal activity in mice, particularly affecting sperm derived from spermatogonial cells. These changes suggest potential antifertility effects and utility in detecting harmful chemicals.
Area of Science:
- Reproductive Toxicology
- Sperm Biology
- Chemical Mutagenesis
Background:
- Mammalian sperm parameters like acrosomal proteolytic activity, motility, and count are crucial indicators.
- These parameters can be used to detect mutagens, carcinogens, developmental toxicants, and antifertility agents.
Purpose of the Study:
- To assess the impact of mitomycin C (MC) on sperm count, motility, and acrosomal proteolytic activity in mice.
- To investigate which sperm cell developmental stages are most sensitive to MC-induced damage.
- To explore the potential of these sperm phenotypes as biomarkers for antifertility effects.
Main Methods:
- Mice received a single intraperitoneal injection of mitomycin C (5 mg/kg) or saline.
- Sperm were collected at 1, 3, 5, 7, and 10 weeks post-injection.
- Sperm parameters (count, motility, acrosomal proteolytic activity) were analyzed from various developmental stages.
Main Results:
- Mitomycin C significantly decreased sperm count, motility, and acrosomal proteolytic activity in sperm derived from preleptotene or spermatogonial cells.
- Sperm derived from spermatogonial stem cells also showed decreased acrosomal proteolytic activity.
- Sperm derived from spermatozoa and spermatids showed no significant decrease in these parameters.
Conclusions:
- Mitomycin C exposure induces sperm dysfunction, primarily impacting sperm originating from spermatogonial cells, suggesting mutational or developmental effects.
- The observed changes in sperm count and acrosomal proteolytic activity may serve as indicators for chemicals with antifertility properties.