Epididymitis: revelations at the convergence of clinical and basic sciences

Abstract

Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

“…Pathogens can reach the epididymis via their retrograde ascent through the urethra. An animal model that mimics that situation is the retrograde injection of bacteria or LPS into the vas deferens lumen (Michel et al, 2015;Silva et al, 2018;Wang et al, 2019), a procedure that increases tissue concentration of cytokines and chemokines in the cauda epididymis (Silva et al, 2018;Wang et al, 2019). Here, we show that CCs rapidly respond to an LPS challenge by upregulating distinct sets of pro-inflammatory chemokines and cytokines, such as Cxcl10, Cxcl1, Cxcl2, Ccl5 and Il6.…”

“…Breakdown of the homeostasis between the epididymal mucosa and sperm might be responsible for a significant number of male infertility cases (McLachlan, 2002). Epididymitis is an inflammatory condition that frequently produces scrotal pain and infertility (Michel et al, 2015). Pathogens can reach the epididymis via their retrograde ascent through the urethra.…”

β-defensins and the epididymis: contrasting influences of prenatal, postnatal, and adult scenarios

“…In a rat epididymitis model induced by Gram-negative bacteria, however, Spag11e ( Bin1b ) mRNA levels decreased 3 days after infection. 32 In other experimental models of epididymitis induced by LPS, Defb2 , Defb21 and Defb27 mRNA levels decreased in the caput epididymidis, 39 40 while other β-defensins such as Defb29 , Defb41 and Defb42 were unaffected by the treatment. 40 Although the abundance of Spag11b ( Bin1b ) mRNA decreased following bacterial infection in the mouse epididymis, 41 its overexpression gave mice added resistance to E. coli -induced epididymitis.…”

“… 28 29 In this context, there are data supporting both anti- and pro-inflammatory roles for β-defensins, 10 28 indicating the need for further studies to uncover their specific roles in the epididymis as modulators of the immune system. How β-defensins communicate and participate with other key innate immunity effectors such as TLR4, humoral mediators (e.g., cytokines, chemokines) and immune cells (e.g., phagocytes and dendritic cells) 30 31 32 in the maintenance of the epididymal function and in the ability of this organ to nurture the spermatozoa in normal and in infectious and inflammatory conditions, are still poorly understood.…”

Expression profile of Toll‐like receptor 4 in rat testis and epididymis throughout postnatal development

“…Bacterial infections are the most frequent etiological factors of male genital tract. Researchers showed that lipopolysaccharides (LPS), major components of the outer membrane of Gram-negative bacteria, induced epididymitis (Michel, Pilatz, Hedger, & Meinhardt, 2015;Silva et al, 2018). However, autoimmune orchitis can occur under certain pathological conditions, such as physical trauma, and exposure to chemical toxins or high temperature that may damage germ cells (Schuppe et al, 2008).…”