Abstract
The epididymis is an important male accessory sex organ where sperm motility and fertilization ability develop. When spermatozoa carrying foreign antigens enter the epididymis, the epididymis shows “immune privilege” to tolerate them. It is well-known that a tolerogenic environment exists in the caput epididymis, while pro-inflammatory circumstances prefer the cauda epididymis. This meticulously regulated immune environment not only protects spermatozoa from autoimmunity but also defends spermatozoa against pathogenic damage. Epididymitis is one of the common causes of male infertility. Up to 40% of patients suffer from permanent oligospermia or azoospermia. This is related to the immune characteristics of the epididymis itself. Moreover, epididymitis induced by different pathogenic microbial infections has different characteristics. This article elaborates on the distribution and immune response characteristics of epididymis immune cells, the role of epididymis epithelial cells (EECs), and the epididymis defense against different pathogenic infections (such as uropathogenic Escherichia coli, Chlamydia trachomatis, and viruses to provide therapeutic approaches for epididymitis and its subsequent fertility problems.
Highlights
Infertility is the third major issue affecting human health, experienced by ∼10–15% of couples when attempting to conceive a baby, among which 50% are related to male factor infertility [1]
This study describes the immune characteristics of the epididymis and the immune pathways of the epididymitis triggered by various pathogenic infections (E. coli, Chlamydia trachomatis, viruses, etc.) in animal models to explore how the immune related-mechanisms of epididymitis can impair male fertility
A recent study has revealed that transforming growth factorβ (TGF-β) signaling in Dendritic cells (DCs) is required for immunotolerance to sperm located in the epididymis, and that male mice lacking TGFβ signaling in DCs would develop severe epididymal inflammation [34]
Summary
Infertility is the third major issue affecting human health, experienced by ∼10–15% of couples when attempting to conceive a baby, among which 50% are related to male factor infertility [1]. Infection and inflammation are involved in 13–15% of cases of male factor infertility. Relevant diseases that can lead to infertility include epididymitis, combined epididymo-orchitis, and rarely, isolated orchitis [4, 5]. Acute epididymitis is one of the most common diseases related to male inflammation. Epididymitis can occur in men of any age. Pilatz et al [7] investigated 237 patients with acute epididymitis aged 18–97 years and found the highest incidence rate was in the group aged between 48 and 57 years old. Redshaw et al [8] showed that the annual incidence of acute epididymitis is ∼1.2/1,000 boys at the age of two to 13 years, while 43% of epididymitis cases occur among adult men aged 20–30 years
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