title: Angiotensin II dependent testicular fibrosis and effects on spermatogenesis after vasectomy in the rat.
abstract: OBJECTIVE
  Vasectomy induces testicular interstitial fibrosis in time dependent fashion and inhibits spermatogenesis. We investigated the contribution of angiotensin II (Ang II) to the development of interstitial fibrosis after vasectomy.
  
  
  METHODS
  Bilateral vasectomy was performed in 8-week-old Wistar rats and the testes were harvested 1 to 24 weeks after vasectomy. Interstitial fibrosis was evaluated by Masson's trichrome staining. Western blotting and immunohistochemistry were done to examine the expressions of heat shock protein 47 (HSP47), HNE (4-hydroxy-2,3-nonenal) and transforming growth factor-beta1 (TGF-beta1). The antioxidative agent N-acetylcysteine (NAC), the Ang II type 1 receptor antagonist losartan or the Ang converting enzyme inhibitor enalapril was given orally for 24 weeks to vasectomized rats. Spermatogenesis was evaluated by testicular weight and the percent of haploid cells was analyzed by flow cytometry.
  
  
  RESULTS
  Vasectomy significantly increased interstitial fibrosis (more than 8 weeks) and induced the expression of HSP47, HNE modified protein and TGF-beta1. TGF-beta1 and HSP47 immunoreactivity was localized to Leydig cells and fibroblasts. NAC or losartan but not enalapril inhibited the expression of these molecules induced by vasectomy. Increased interstitial fibrosis and impaired spermatogenesis were partially abrogated by NAC or losartan administration.
  
  
  CONCLUSIONS
  There is Ang II type 1 receptor dependent fibrosis after vasectomy. Oxidative condition is considered to trigger and promote these fibrogenic processes. Ang II contributes to the regulation of intratesticular autocrine or paracrine functions after vasectomy.
authors.affiliation: Department of Urology and Forensic Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan. k-siraisi@simo.saiseikai.or.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujimiya
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Naito
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005355:Fibrosis / Q000473:pathology; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects / Q000473:pathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology*; D013737:Testis / Q000187:drug effects / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014659:Vasectomy
chemical_list: D000447:Aldehydes; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494662:Serpinh1 protein, rat; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C462359:tert-4-hydroxy-2-nonenal; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan; D000111:Acetylcysteine