Spermatic Granuloma and Inflammatory Reactions in Epididymis of Adult Rats following Testosterone Depletion

Abstract

Depletion of testosterone (T), vasectomy or chemical insults are known to induce spermatic granuloma (SG) in epididymis, however, the exact mechanisms are unknown. We treated adult male rats with a Leydig cell specific toxicant ethylene dimethane sulfonate (EDS) to deplete T, causing SG formation in epididymis. Histological evaluation revealed the presence of testicular germ cells (TGC) in the caput of epididymis which were apoptotic. An increased proportion of tubular epithelial cells in caput were also apoptotic. Immunofluorescent staining showed extensive infiltration of monocytes/macrophages around the periphery of the shrunken tubules and SG. CD4+ and CD8+ lymphocytes were also detected inside the tubules and SG. In confirmation, quantitative real time PCR for mRNA of macrophage marker CD68, and lymphocyte markers CD4 and CD8 were increased in EDS treated epididymis compared to controls (19 fold, 3.5 fold and 7.5 fold respectively). Aquaporin 9 mRNA increased 11 fold in EDS treated epididymis which may be indicative of restricted testicular fluid flow into epididymis. These pathological conditions were reversed after T replacement in EDS treated rats. Thus, our data indicates that influx and accumulation of apoptotic TGCs in the epididymis due to the disintegration of the blood‐testis barrier and disruption of testicular fluid flow into epididymis may play a role in SG formation.