Deoxyribonucleic acid repair and apoptosis in testicular germ cells of aging fertile men: the role of the poly(adenosine diphosphate-ribosyl)ation pathway
Received 7 December 2007; received in revised form 9 March 2008; accepted 11 March 2008. published online 28 April 2008.
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-complementing1(XRCC1), and apurinic/apyrimidinic endonuclease 1 (APE1)]; 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 APE1), 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.
aDepartment of Dermatology, Sexually Transmitted Diseases and Andrology, Al-Minya Faculty of Medicine, Al-Minya, Egypt
bDepartment of General Surgery, Al-Minya Faculty of Medicine, Al-Minya, Egypt
cDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
Reprint requests: Denny Sakkas, Ph.D., Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven, CT 06520-8063 (FAX: 203-785-7134).
M.M.E.-D. has nothing to disclose. A.-B.M.A.D. has nothing to disclose. M.T.B. has nothing to disclose. H.M.E.-F. has nothing to disclose. J.X. has nothing to disclose. D.S. has nothing to disclose.
Dr. El-Fakahany was supported by a fellowship from the Egyptian Cultural and Educational Bureau.
Presented in part at the 22nd Annual Meeting of the European Society of Human Reproduction and Embryology, June 18–21, 2006, Prague, Czech Republic.
ABSTRACT