title: Cyclooxygenase-2 protects germ cells against spermatogenesis disturbance in experimental cryptorchidism model mice.
abstract: The role of cyclooxygenases (COX) in the male reproductive organ remains unclear. However, there are some reports suggesting that COX-2 might have an effect on spermatogenesis or steroidogenesis. In this study, we examined whether COX-2 was induced in impaired testes, and we also investigated the possible role of COX in the testes using experimental cryptorchidism model mice. Five-week-old male mice underwent an operation to induce unilateral cryptorchidism via an abdominal incision and suturing of the left testes to the lateral abdominal wall, and they were then divided into 3 groups: 1) experimental cryptorchidism plus SC560 (selective COX-1 inhibitor) administration; 2) experimental cryptorchidism plus NS398 (selective COX-2 inhibitor) administration; 3) and experimental cryptorchidism alone. The expression levels of COX-1 and COX-2 were determined by immunohistologic staining and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The influence of COX inhibitors on the testes was assessed by measuring the concentration of serum testosterone and evaluating the seminiferous tubules according to the Johnsen score. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining was also performed to detect apoptosis in the testes. Immunohistologic staining and RT-PCR revealed that the expression of COX-2 was increased in the experimental cryptorchid testes (groups 1-3). The concentration of serum testosterone was significantly lower in group 2 at 5 weeks after surgery than in the other groups. The Johnsen score of the cryptorchid testes in group 2 was significantly lower than those in other groups at 5 weeks after surgery. TUNEL staining revealed that the number of apoptotic cells was significantly increased in group 2 compared with the other groups. However, the COX-1 inhibitor did not appear to affect spermatogenesis in the experimental cryptorchid testes. These results suggest that the COX-2 inhibitor provoked testicular damage in experimental cryptorchidism by inducing germ cell apoptosis. The expression of COX-2 might be induced to protect germ cells from heat stress caused by experimental cryptorchidism.
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kubota
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kubota
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Umemoto
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Yanai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tozawa
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003456:Cryptorchidism / Q000473:pathology / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009578:Nitrobenzenes / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013091:Spermatogenesis / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D015232:Dinoprostone