Nitric oxide produced in the testis is involved in dilatation of the internal spermatic vein that compromises spermatogenesis in infertile men with varicocele


Koji Shiraishi, Department of Pharmacology, the University of Iowa, 2–310 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242, USA.



To determine the concentration of nitric oxide (NO) and the location and change in the expression of NO synthase (NOS) isoforms in the testes of subfertile men with varicocele, and to compare the NO concentration or NOS expression with clinical variables, to determine the role of NO on the pathophysiology of varicocele.


In all, 27 men who had a left varicocelectomy and five with ‘normal’ spermatogenesis (controls) who had scrotal surgery for other reasons were enrolled. Intratesticular fluid was taken from the men and the NO concentration determined colorimetrically. The expression and location of NOS isoforms were examined by Western blotting and immunohistochemistry, using testicular biopsy specimens, and NADPH-diaphorase (NADPH-d) staining used to identify NO-producing cells. The relationship between the NO concentration and the expression of NOS isoforms or clinicopathological variables was investigated.


In testes with grade 2 and 3 varicoceles there were significant increases in the concentration of NO or the expression of inducible NOS. There was no change in the expressions of endothelial NOS, which is located in vascular endothelial cells, while NADPH-d activity was mainly located in these cells. The concentration of NO was significantly correlated with the maximum and total vein diameter (both P < 0.01). In patients aged >35 years, the concentration of NO significantly correlated with a deterioration in total motile sperm count (P < 0.05).


Increased production of NO in the testis is involved in the enlargement of varicocele and indirectly deteriorates spermatogenesis.