Epididymitis is a leading cause of male reproductive disease and infertility. Our previous studies in a bacterial epididymitis model revealed that the cauda epididymis was severely damaged by fibrosis, while the caput region remained relatively intact. The caput epididymis, where spermatozoa are first exposed to the immune system outside the immune-privileged testis, contains numerous immunoregulatory cells (dendritic cells, macrophages) and genes, such as activin A (Inhba), activin B (Inhbb), and indolamine 2,3,deoxygenase-1 (Ido1). These immunological parameters were considerably reduced in the cauda, where spermatozoa are stored prior to ejaculation.
A murine model of experimental autoimmune epididymo-orchitis was used to investigate the regional differences in the immune response. Adult C57/Bl6 mice were immunised with syngeneic testicular homogenates in adjuvant (s.c. 3x, fortnightly). Controls received adjuvant only, or were untreated. Tissues were collected 50 days following the first immunisation.
All animals that developed orchitis also showed epididymitis, but epididymitis alone was observed in some animals. Epididymitis was characterized by epithelial damage, immune cell infiltrates and fibrosis in the cauda. In extreme cases, sperm were observed in the interstitium. The caput appeared relatively normal in all animals. Based on histopathology and cytokine expression, a damage score ranging from 0-5 was established (0 = normal, 5 = severe epididymitis). The severity of orchitis and epididymitis were positively correlated. The expression of genes important in epididymal immunoregulation and inflammation, including Ido1, Foxp3, Tnf, Il1b, Il10, Tgfb1 and Ccl2, correlated with the damage score in the cauda. Only a minor upregulation of genes was seen in the caput.
These data indicate that the caput and cauda have very different immunological environments. We postulate that the caput is more tolerogenic/anti-inflammatory to protect immunologically ‘foreign’ sperm from the body’s immune system, while the cauda is primed to combat ascending infections, and is therefore more susceptible to inflammation.