Case Report: Dendritic Cells and Macrophages Capture Sperm in Chronically Inflamed Human Epididymis

Abstract

Chronic inflammation of the male genital tract is thought to be a primary etiological factor of male infertility. The abundance and activation of macrophages and dendritic cells in patients with chronic inflammation of genital tract were closely associated with oligozoospermia and asthenospermia. Chronic epididymitis appears to be more important than seminal vesiculitis or prostatitis due to the direct interaction between spermatozoa and epididymal inflammatory cells. In this study, we present a case report of a 41-year-old male with oligoasthenospermia and chronic epididymitis. Hematoxylin-eosin staining and immunofluorescence analyses showed that antigen presenting cells including macrophages and dendritic cells were found capturing spermatozoa in the lumen of cauda epididymis. To our knowledge, this is the first case report that directly observed dendritic cells capturing spermatozoa in the lumen of an inflamed epididymis. This finding directly explains chronic epididymitis as the possible cause of oligospermia in patients.

The enigmatic interplay of immune cells and abnormal spermatozoa through Mendelian randomization

“…The findings suggest a probable strong association between the prevalence of seminal macrophages in rabbit semen and diminished spermatozoa quality 29 . Moreover, the quantity and activation state of macrophages and dendritic cells among individuals with chronic genital tract inflammation were found to be significantly correlated with conditions of oligozoospermia and asthenospermia 30 …”

“…29 Moreover, the quantity and activation state of macrophages and dendritic cells among individuals with chronic genital tract inflammation were found to be significantly correlated with conditions of oligozoospermia and asthenospermia. 30 At the same time, three immune cell types might act as protective factors against the occurrence of abnormal spermatozoa.…”

Exploring the role of gut microbiome in male reproduction

“…In conclusion, bacterial translocation may result in an excessive immunological response and a chronic inflammatory status, which can induce endothelial injury, disruption of the blood–testis barrier (BTB), and impaired spermatogenesis and viability 18 . Moreover, the infiltration of activated macrophages and dendritic cells into the epididymis lumen might trap normal spermatozoa and induce immunological damage 19 . The “leaky gut” hypothesis also links endotoxin with hypogonadism, where endotoxin can inhibit steroid hormone synthesis in Leydig cells and reduce pituitary luteinizing hormone drive resulting in reducing testosterone production, ultimately leading to a reduction in spermatozoa 20 …”

“…18 Moreover, the infiltration of activated macrophages and dendritic cells into the epididymis lumen might trap normal spermatozoa and induce immunological damage. 19 The "leaky gut" hypothesis also links endotoxin with hypogonadism, where endotoxin can inhibit steroid hormone synthesis in Leydig cells and reduce pituitary luteinizing hormone drive resulting in reducing testosterone production, ultimately leading to a reduction in spermatozoa. 20 This might also explain why nonalcoholic fatty liver disease (NAFLD) can cause hypogonadism in men because of the increased intestinal permeability and tight junction alterations in patients with NAFLD compared to healthy individuals.…”

Gut microbiota supports male reproduction via nutrition, immunity, and signaling

“…In the case of disturbed GM, the secretion of pro-inflammatory factors increases activating macrophages and dendritic cells in the testis. When these innate immune cells enter the epididymis, sperms are recognized as non-self substances attacked, affecting their survival and function ( Zheng et al, 2021 ).…”