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


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.
Department of Anatomy, College of Medicine, Chosun University, Gwangju, Republic of Korea.
In-Youb
IY
Chang
Jin-Ho
JH
Kim
Kyeong-Han
KH
Park
Sang-Pil
SP
Yoon
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D006657:Histones / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013090:Spermatocytes / Q000378:metabolism* / Q000473:pathology; D013093:Spermatogonia / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014646:Varicocele / Q000378:metabolism* / Q000473:pathology
D006657:Histones; D016159:Tumor Suppressor Protein p53