Disturbance of spermatogenesis and apoptosis

• Project/Area Number: 09470350
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: SASAKI Shoichi Nagoya City University, Medical School, Assistant professor, 医学部, 講師 (50225869)
• Co-Investigator(Kenkyū-buntansha): KOHRI kenjiro Nagoya City University, Medical School, Professor, 医学部, 教授 (30122047) ; HAYASHI Yutaro Nagoya City University, Medical School, Assistant professor, 医学部, 講師 (40238134) ; 山田 泰之 名古屋市立大学, 医学部, 助手 (60264735)
• Project Period (FY): 1997 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥11,400,000 (Direct Cost: ¥11,400,000); Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000); Fiscal Year 1997: ¥6,100,000 (Direct Cost: ¥6,100,000)
• Keywords: Disturbance of spermatogenesis / Apoptosis / Nuclear factor-kappa B / Rat / Testis / P53 / NO / Calpain / Nuclear factor-kappaB / 造精障害 / Nuclear Factor kappa B / N-acetyl-l-cystein

Research Abstract

The spermatogenesis is hindered by various stresses. It is reported that the apoptosis is concerned in the spermatogenesis failure. Using the rat in each following experimental model, we examined the expression of the apoptosis and involvement of transcription factor nuclear factor-kappa B(NFκB) for the disorder of spermatogenesis. 【encircled1】 cryptorchidism (model rat of high temperature environment of testicles which fixed the testicles of the maturation rat in the peritoneal cavity and cryptorchidism rat made by administering Flutamide for the fetal stage 【encircled2】 torsion of thespermatic cord (unilateral and bilateral) 【encircled3】 the obstruction of seminal tract cord (unilateral and bilateral) 【encircled4】 the chemical castration (leuprolerin acetate 3mg/kg administration) 【encircled5】 diethylstilbesterol (500μg/body x 28days) administration 【encircled6】 testicular trauma cord (unilateral and bilateral)
The testes of either model caused the atrophy of which was more significan t than the controls, and the expression of large number of apoptotic cells was recognized in the process. In the unilateral model of 【encircled2】,【encircled3】 and 【encircled6】, the apoptosis was also recognized in the contra-lateral tedticles, and it considered that the apoptosis was related with the crisis of the autoimmune orchitis. In 【encircled2】 the calpain which was the calcium-dependent cysteine protease increased, and calpain production and apoptosis expression were suppressed by the antioxidant. In 【encircled3】 the expression of the NOS increased with the increase in the apoptosis cell. In each model the conversion of NFκB to the nucleus and the expression of the p53 protein were observed with the apoptosis expression. In addition, the nucleus internal transportation of NFκB was suppressed, and the apoptosis expression was strengthened when the inhibitor of NFκB was administered in 【encircled4】 and 【encircled5】.
From the above results, it was considered that NFκB had been activated in the normal rat testicular cells, and it might suppress the apoptosis. The suppression of the NFκB activity seemed to be concerned in the strong expression of the apoptosis in the disturbance of the spermatogenesis.