Vasectomy impairs spermatogenesis through germ cell apoptosis mediated by the p53-BAX pathway in rats

Purpose: The pathophysiology of impaired spermatogenesis after vasectomy ha s not been completely investigated. We examined the role of p53 protein in cell cycle arrest and apoptosis of germ cells after vasectomy in the rat. Materials and Methods: Eight-week old rats underwent bilateral vasectomy an d the testes were harvested 1, 4, 8, 12 and 24 weeks after surgery. Germ ce ll apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediate d deoxyuridine triphosphate nick end-labeling (TUNEL) and electrophoresis a ssay of DNA fragmentation. Western blot analysis and immunohistochemistry w ere performed to examine the expression of p53, proliferating cell nuclear antigen, Bax, Bcl-2, p21WAF1/Cip1 and Gadd45. To evaluate spermatogenesis, testicular weight and percent of haploid cells flow cytometry was done. Results: Spermatogenesis impairment was associated with increased p53 and d ecreased proliferating cell nuclear antigen expression at the delayed phase more than 8 weeks after vasectomy. The number of TUNEL positive germ cells was increased at the early 1-week and delayed phases after vasectomy. Bax but not p21WAF1/Cip1 or Gadd45 expression was increased. p53, Bax and TUNEL positive cells were co-localized in the seminiferous tubules. Conclusions: Spermatogenesis was impaired after vasectomy by apoptosis but not by cell cycle arrest. The p53-Bax pathway effects apoptosis in the dela yed phase after vasectomy in some seminiferous tubules.