Ethylene dimethane sulfonate (EDS) ablation of Leydig cells in adult rat depletes testosterone resulting in epididymal sperm granuloma: Testosterone replacement prevents granuloma formation

Sperm granuloma may develop in the epididymis following vasectomy or chemical insults. Inflammation due to sperm granuloma causes abdominal and scrotal pain. Prolonged and persistent inflammation in the epididymis due to sperm granuloma may lead to infertility. Extravasation of germ cells into the interstitium of epididymis following damage of the epididymal epithelium is one of the primary reasons for sperm granuloma-associated pathology. Since testosterone is vital for the maintenance of epididymal epithelium, we investigated the pathology of sperm granuloma and its relationship with testosterone. Adult rats were treated with a Leydig cell-specific toxicant ethylene dimethane sulfonate (EDS) to eliminate testosterone. At 7 days post-EDS, disrupted epididymal epithelium and sperm granuloma were observed in the caput epididymis. Sperm granuloma and caput were collagen-filled indicating fibrosis. Numerous round apoptotic cells were localized inside the caput lumen and dispersed through the sperm granuloma. Tnp1 (round spermatid marker) was significantly higher in the epididymis of the EDS-treated group compared to controls suggesting the apoptotic cells were round spermatids. Increases in CD68⁺ macrophages and T cells (CD4 and CD8) support an inflammatory immune infiltration in post-EDS epididymis. However, testosterone replacement following EDS prevented the sperm granuloma-associated pathology. We suggest that the immune response in the sperm granuloma may be due to the increased numbers of apoptotic round spermatids or other testicular tissue components that may be released, in addition to the regression of epididymal epithelium due to testosterone loss. Thus, testosterone replacement prevents EDS-induced sperm granuloma and ameliorates sperm granuloma-associated pathology.