Urogenital tract inflammation and male fertility: from human disease to animal models and viceversa

MOTRICH, RUBEN D.

Varadero

Congreso; 13th Latin American and Caribbean Congress of Immunology ? ALACI21/22; 2022

The prostate is the target of disorders that affect men of all ages. Pathologies range from infection, to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), to benign hyperplasia and cancer. CP/CPPS is a prevalent disease affecting men younger than 50 years and characterized by pelvic pain and chronic inflammation of the prostate of unknown etiology. Autoimmune responses against prostate antigens were revealed in CP/CPPS patients. In fact, self-reactivity of Th1 cells to prostate and seminal plasma proteins were detected in a considerable proportion of patients in the absence of infection. These autoimmune responses were associated with elevated levels of inflammatory cytokines and chemokines, and leukocyte subpopulations in semen. Interestingly, striking alterations in sperm quality of these patients were also reported. Besides, rodent models of experimental autoimmune prostatitis (EAP) have allowed an important advance in the understanding of human disease. After immunization, animals developed specific Th1/Th17 cell-mediated responses that caused severe histopathology in the prostate and the induction of chronic pelvic pain. In fact, INFγ has shown to be critical to confer pathogenic T cells the capability of homing to the prostate, where they induced leukocyte recruitment and inflammatory cytokine release and pelvic pain development. Moreover, autoimmune animals showed striking alterations in sperm quality and increased oxidative stress that were associated with a significant reduction in their male fertility potential. Altogether, our results support the notion that an autoimmune response to prostate antigens may be the underlying cause of CP/CPPS. Moreover, chronic inflammation of the prostate may seriously compromises male fertility potential.