Epididymitis, a frequent urological disease commonly caused by bacterial infections, results in inflammation and fibrosis, which may lead to chronic autoimmune pathology. Normally, dendritic cells, macrophages and expression of immunoregulatory genes, such as activin A (Inhba), activin B (Inhbb), and indolamine 2,3,deoxygenase-1 (Ido1) are prominent in the caput epididymis, located adjacent to the testis. In contrast, these immunological parameters are considerably reduced in the cauda epididymis, where sperm are stored prior to ejaculation. We used an established murine model of experimental autoimmune epididymo-orchitis to study the histopathology and inflammatory gene changes in autoimmune epididymitis, with particular focus on regional differences.
Adult C57/Bl6 mice were immunised (s.c. 3 times, 14 days apart) with testicular homogenates (TH) from syngeneic mice in adjuvant (Complete Freund’s adjuvant and Incomplete Freund’s adjuvant), together with 100 ng of Bordetella pertussis toxin i.p. Controls received adjuvant only, or were untreated. Tissues were collected 30 and 50 days following the first immunisation.
A large animal-to-animal variation was observed in the response to immunisation with TH. All animals that developed orchitis also showed epididymitis, while epididymitis alone was observed in some animals, suggesting that epididymitis precedes orchitis in this model. Histopathological examination of the epididymis revealed varying degrees of epithelial damage, leading to sloughing of epithelial cells into the lumen, interstitial immune cell infiltrates and fibrosis. In extreme cases, interstitial sperm aggregates were observed. Based on histopathology, a damage scoring system ranging from 0-4 was designed (0 = normal epididymis, 4 = severe epididymitis). The cauda was the most affected region, while the caput appeared relatively normal. The expression of genes important in epididymal immunoregulation and inflammation, including Inhba, Inhbb, Ido1, Tnf and Ccl2, correlated with the damage score. No changes in gene expression was observed at 30 days. At 50 days, only a mild upregulation of genes was seen in the caput of animals with a high damage score. In the cauda, however, all genes were considerably increased in animals with a damage score of 3-4.
These data suggest that the caput and cauda have different immunological environments. We postulate that this is because the caput is more tolerogenic 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 and subsequent damage.