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Spermatogenic cell apoptosis induced by mitomycin C in the mouse testis
S Nakagawa1, N Nakamura, M Fujioka
1Department of Anatomy and Developmental Biology, Faculty of Medicine, Kyoto University, Japan.
Abstract:
Spermatogenic cell degeneration in the mature mammalian testis occurs both spontaneously during normal spermatogenesis and in response to cytotoxic agents. Mitomycin C (MC) is an antibiotic that affects DNA synthesis. In the present study, we examined the induction of mouse spermatogenic cell apoptosis by MC, using TdT-mediated dUTP-biotin nick end labeling (TUNEL) to detect high levels of DNA fragmentation in situ, transmission electron microscopy (TEM) to observe nuclear chromatin condensation, and molecular methods to detect DNA ladders. This study shows that in the testis of MC-treated mice: (i) apoptotic cell death with fragmentation of nuclear DNA is induced by MC dose-dependently, (ii) apoptotic cell death is most commonly found in the spermatogonia and less frequently in spermatocytes, and (iii) apoptotic cell death induced by MC is not specific for the seminiferous stage of the tubules. The present study suggests that the spermatogenic cell apoptosis induced by MC might be involved in its testicular toxicity.
Insights
Mitomycin C (MC) induces apoptosis in mouse spermatogenic cells in a dose-dependent manner, primarily affecting spermatogonia. This finding suggests MC
Area of Science:
- Reproductive biology
- Toxicology
- Cell biology
Background:
- Spermatogenic cell degeneration occurs spontaneously and due to cytotoxic agents.
- Mitomycin C (MC) is an antibiotic known to affect DNA synthesis.
Purpose of the Study:
- To investigate the induction of apoptosis in mouse spermatogenic cells by Mitomycin C.
- To characterize the dose-dependency and cell-type specificity of MC-induced apoptosis.
Main Methods:
- TdT-mediated dUTP-biotin nick end labeling (TUNEL) for DNA fragmentation.
- Transmission electron microscopy (TEM) for chromatin condensation.
- Molecular methods for detecting DNA ladders.
Main Results:
- MC induced apoptotic cell death with DNA fragmentation dose-dependently.
- Apoptosis was most common in spermatogonia, less frequent in spermatocytes.
- MC-induced apoptosis was not specific to any seminiferous tubule stage.
Conclusions:
- MC induces spermatogenic cell apoptosis in mice.
- The observed apoptosis may contribute to the testicular toxicity of MC.