Expression of Endothelial Nitric Oxide Synthase in Testicular Cells of Men with Obstructive Azoospermia; a Case-Control Study
Introduction: Obstructive azoospermia is one of the causes of post-testicular infertility in men and previous studies have reported inconsistent levels of endothelial nitric oxide synthase (eNOS) enzyme in these patients. Accordingly, the present study aimed to provide further evidence on the expression of eNOS enzyme in patients with azoospermia. Materials and Methods: In this case-control study, 10 patients, who were diagnosed with azoospermia and were referred to the infertility center for treatment or diagnosis, and 7 healthy fertile men were recruited. An informed written consent was obtained from included subjects and they underwent testicular biopsies. Samples were assessed via immunohistochemical methods to determine their levels of eNOS expression.Results: Both leydig and sertoli cells were found to express eNOS, while this enzyme was not expressed in normal germinal cells. The only significant difference between the two groups was the level of eNOS expression in sertoli cells which was found to be higher in patients with obstructive azoospermia compared to the control group (P<0.001). Conclusion: According to the results of this study, sertoli cells and their interactions with germinal cells of seminiferous tubule might play an important role in sperm quality and a subsequent successful fertilization.
Irvine DS. Epidemiology and aetiology of male infertility. Human reproduction. 1998;13(suppl_1):33-44.
Stanwell‐Smith R, Hendry W. The Prognosis of Male Subferility: a Survey of 1025 Men Referred to a Fertility Clinic. BJU International. 1984;56(4):422-8.
Battaglia C, Giulini S, Regnani G, Madgar I, Fac-chinetti F, Volpe A. Intratesticular Doppler flow, seminal plasma nitrites/nitrates, and nonobstructive sperm extraction from patients with obstructive and nonob-structive azoospermia. Fertility and sterility. 2001;75(6):1088-94.
Nistal M, Riestra M, Galmés-Belmonte I, Paniagua R. Testicular biopsy in patients with azoo-spermia. Am J Surg Pathol. 1999;23(12):1586-54.
Ezeh U, Moore H, Cooke I. Correlation of testic-ular sperm extraction with morphological, biophysical and endocrine profiles in men with azoospermia due to primary gonadal failure. Human reproduction (Oxford, England). 1998;13(11):3066-74.
Shiraishi K, Naito K. Nitric oxide produced in the testis is involved in dilatation of the internal spermatic vein that compromises spermatogenesis in infertile men with varicocele. BJU international. 2007;99(5):1086-90.
Doshi SB, Khullar K, Sharma RK, Agarwal A. Role of reactive nitrogen species in male infertility. Re-productive Biology and Endocrinology. 2012;10(1):109.
Fujisawa M, Yamanaka K, Tanaka H, Okada H, Arakawa S, Kamidono S. Expression of endothelial nitric oxide synthase in the Sertoli cells of men with infertility of various causes. BJU international. 2001;87(1):85-8.
Zini A, O'Bryan MK, Magid MS, Schlegel PN. Immunohistochemical localization of endothelial nitric oxide synthase in human testis, epididymis, and vas deferens suggests a possible role for nitric oxide in spermatogenesis, sperm maturation, and programmed cell death. Biology of reproduction. 1996;55(5):935-41.
Burnett AL, Ricker DD, Chamness SL, Maguire MP, Crone JK, Bredt DS, et al. Localization of nitric oxide synthase in the reproductive organs of the male rat. Biology of Reproduction. 1995;52(1):1-7.
Moncada S, Palmer R, Higgs E. Nitric oxide: physiology, pathophysiology, and pharmacology. Phar-macological reviews. 1991;43(2):109-42.
Schmidt HH, Walter U. NO at work. Cell. 1994;78(6):919-25.
Foghi K, Novin MG, Jabbari ZM, Najafi T, Heidari MH, Yasoori AR. Immuno-histochemical localization of endothelial nitric oxide synthase in testicular cells of men with non-obstructive azoospermia. Iranian journal of reproductive medicine. 2011;9(4):277.
Middendorff R, Muller D, Wichers S, Holstein A, Davidoff M. Evidence for production and functional ac-tivity of nitric oxide in seminiferous tubules and blood vessels of the human testis. The Journal of Clinical En-docrinology & Metabolism. 1997;82(12):4154-61.
Shaul PW, North AJ, Wu LC, Wells LB, Brannon TS, Lau KS, et al. Endothelial nitric oxide synthase is expressed in cultured human bronchiolar epithelium. Journal of Clinical Investigation. 1994;94(6):2231.
Ishikawa T, Kondo Y, Goda K, Fujisawa M. Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism. Journal of andrology. 2005;26(2):281-8.
Lee NP, Cheng CY. Nitric oxide/nitric oxide syn-thase, spermatogenesis, and tight junction dynamics. Biology of reproduction. 2004;70(2):267-76.
Koppenol W, Moreno J, Pryor WA, Ischiropoulos H, Beckman J. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chemical research in toxicology. 1992;5(6):834-42.
Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. 2009.
Based on the obtained author agreement upon submission, "Shahid Beheshti University of Medical Sciences" is the copyright owner of the published material. However, according to Bethesda Statement, all works published in this journal are open access and freely available to anyone on the journal web site without cost under creative common license BY-NC. Based on this license, under the condition of proper citation, “Emergency” grants to all users the following rights:
1. Free, irrevocable, worldwide, perpetual access to all published materials.
2. To copy, use, distribute, transmit and display the work on third party repositories and social media.
3. To make and distribute derivative works in any digital medium for any non-commercial purpose.