Deoxyribonucleic acid repair and apoptosis in testicular germ cells of aging fertile men: the role of the poly(adenosine diphosphate-ribosyl)ation pathway

Objective: To explore the relationship between men's age and DNA damage repair proteins related to apoptosis in human testicular germ cells. Design: Retrospective case-control study. Setting: Academic institutions. Patient(S): Testicular specimens were obtained from 22 fertile volunteers aged 20-82 years. Intervention(S): Deoxyribonucleic acid repair markers were assessed using immunohistochemical staining for the cell proliferation marker [proliferating cell nuclear antigen (PCNA)]; DNA repair markers [poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1), poly(adenosine diphosphate-ribose) (PAR), X-ray repair cross-complementing 1(XRCC1), and apurinic/apyrimidinic endonuclease I (APE])]; and apoptosis-associated markers (caspase 9, active caspase 3, and cleaved PARP-1). Main Outcome Measure(S): The prevalence and cellular localization of the above markers in testicular tissues of young, middle aged, and old men. Result(s): Statistically significant differences in DNA damage repair-associated proteins (PARP-1, PAR, XRCC1, and APEI), and apoptosis markers (caspase 9, active caspase 3, and cleaved PARP-1) were observed in testicular samples from older men. These differences were most marked in spermatocytes. Conclusion(S): The study demonstrates that there is an age-related increase in human testicular germ cell DNA break repair and apoptosis with age. (Fertil Steril (R) 2009;91:2221-9. (C) 2009 by American Society for Reproductive Medicine.)