Up regulation of nitric oxide nitric-oxide synthase system in the testis of rats with autoimmune orchitis

JARAZO DIETRICH S; JACOBO P; PÉREZ C; LUSTIG L; THEAS MS

Atenas

Congreso; VI Congreso Europeo de Andrología; 2010

Academia Europea de Andrología

Introduction: Experimental Autoimmune Orchitis (EAO) is a model of chronic inflammation characterized by an interstitial cell infiltrate of lymphomonocytes and apoptosis of germ cells. The aim of this work was to characterize nitric oxide (NO)-NO synthase (NOS) system in the testis of EAO rats. NO, a free radical that modulates immune system activation and cell death, is synthetized by the enzymatic conversion of the L-arginine to L-citrulline catalyzed by the constitutive (endothelial and neuronal) and inducible NOS isoforms. Materials and Methods: EAO was induced in rats by active immunization with spermatic antigens and adjuvants, control (C) rats were immunized with saline and adjuvants, normal (N) rats were also studied. Expression of NOS in the testis was detected by immunohistochemistry and flow cytometry (FC) and NOS activity was determined measuring NO and the conversion of [3H]L-arginine to [3H]L-citrulline. Results: In EAO, a higher expression of the three NOS isoforms was observed in the seminiferous tubules, and in the interstitium. Testis from EAO rats produced significantly more NO than C and N rats (µM/mg prot, N: 0.27±0.04, C: 0.30±0.09, EAO: 0.90±0.13, p=0.01 mean±SEM) and the total testicular NOS activity undergo a two fold increase. EAO testicular macrophages produced significantly higher NO levels than C and N macrophages. By FC we observed that the number of ED1+ED2+ macrophages (the predominant subset in EAO) expressing endothelial NOS was significantly increased in EAO vs C and N rats. Conclusions: Results suggest that NO overproduction during EAO development is involved in the pathogenesis of testicular damage.