Region-specific immune responses to autoimmune epididymitis in the murine reproductive tract

Epididymitis is a common pathology of the male reproductive tract, potentially leading to infertility. Studies on bacterial epididymitis indicate that the cauda epididymis is more susceptible to inflammatory damage than the caput. These regional differences in immunoregulation are further investigated using an experimental autoimmune epididymo-orchitis model. Adult mice were immunized against testicular antigens and tissues were collected at 30 and 50 days following the first immunization. Epididymitis developed progressively; 70% of the mice developed disease at 30 days after the initial immunization and 93% at 50 days. Epididymitis was characterized by epithelial damage, immune cell infiltrates and fibrosis in the cauda, with minimal changes in the corpus, while the caput was unaffected. The incidence of epididymitis was greater than that of orchitis but similar to vasitis. The severity of epididymitis was positively correlated with the orchitis severity. Expression of key genes implicated in epididymal immunoregulation, inflammation and fibrosis, such as Ido1, Tnf, Tgfb1, Ccl2, Il1b, Il10, Cx3cl1 and Col1a1, was unchanged in the caput but increased in proportion to damage severity in the cauda at 50 days. Activin receptor mRNA expression in the cauda was negatively correlated with disease severity. These data suggest that the cauda is highly susceptible to inflammatory damage following an autoimmune challenge but the caput is minimally affected. This may be because the cauda is required to combat ascending infections through a robust inflammatory response, while the caput provides a more tolerogenic environment in order to protect the auto-antigenic sperm released from the testis.