Comparative analysis of spermatogenesis and hormonal profile of infertile patients with idiopathic orchitis versus rats with autoimmune orchitis

Abstract

Experimental autoimmune orchitis (EAO) is a well-established rodent model of organ specific autoimmunity associated to infertility. Testis immunopathology is similar in rats and humans undergoing a chronic testicular inflammation. A comparative analysis of other aspects of the disease like the quantification of spermatogonia (Spg) and Sertoli cells (SCs), by immunohistochemistry, as well as the hormonal serum profile of infertile patients with idiopathic orchitis vs rats with EAO was undertaken (RIA). We evaluated testicular biopsies from patients with idiopathic non-obstructive azoospermia, diagnosed with hypospermatogenesis (mild: n=8, severe: n=10) (HypE) and Sertoli cell only syndrome (SCOS, n=9). All groups displayed twice the number of immune cells (CD45+) vs patients with obstructive azoospermia and complete spermatogenesis (control group, C, n=8). The number of undifferentiated and differentiated SPg/seminiferous tubule (ST) decreases in mild and severe HypE while the number of SCs/STs increases in severe HypE and SCOS vs. control (p<0.01). In EAO undifferentiated Spg (CD9+) increased in focal and decreased in severe EAO vs. normal (N) rats. Differentiated SPg (c-Kit+)/ST decreases (mean±SEM, N:10.5±0.3, focal EAO:4.4±0.1, severe EAO:3.1±0.3, p<0.05, n=3) and the SCs/STs number increases vs. N (mean±SEM, N:10.14±1.13, focal EAO:17.32±2.24, severe EAO:19.5±3.5, p<0.05, n=3). FSH, was higher in severe HypE vs C and also in severe EAO vs N. Testosterone and LH were similar to C in severe HypoE and also in severe EAO vs N. Prolactin in mild and severe HypoE was similar to C and in focal and severe EAO was similar to N (mean±SEM ng/ml, N:13.1±2.0, focal EAO:10.2±1.8, severe EAO:14.9±2.8, n=11).We showed that particularly the late stages of EAO closely reflect Spg and SCs behavior, and hormonal profile observed patients with severe HypE. These results validate EAO as a valuable model for studying the impact of inflammatory processes on spermatogenesis.