Experimental varicocele induces p53-dependent germ cell apoptosis through activation of γ-H2AX.

Abstract

AIM: Since DNA damage-related apoptosis is raising concerns regarding abnormal spermatogenesis, we investigated the changes in γ-H2AX during testicular germ cell apoptotic responses in the varicocele model. MATERIALS AND METHODS: Varicocele was induced by partial ligation of the left renal vein and animals were sacrificed at 1, 3, and 4 weeks after varicocele creation. The levels of activated p53 and γ-H2AX formation were determined by Western blot analysis and immunohistochemistry. RESULTS: γ-H2AX formation was augmented after varicocele creation, while a significant increase in p53 phosphorylation was detected in a time course-dependent manner. Varicocele-dependent nuclear γ-H2AX staining in the primary spermatocytes was prominent as degenerative foci, while little differences could be detected in spermatogonia. CONCLUSIONS: These results show that experimental varicocele may induce p53-dependent apoptosis through activation of γ-H2AX in the primary spermatocytes, and suggest that γ-H2AX may be related to apoptotic signal transduction in experimental varicocele.