Spermatogenic cell apoptosis induced by mitomycin C in the mouse testis.
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.
Nakagawa
S
S
Department of Anatomy and Developmental Biology, Faculty of Medicine, Kyoto University, Japan.
Nakamura
N
N
Fujioka
M
M
Mori
C
C
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016685:Mitomycin / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin; D004247:DNA