Chronic inflammation of the male genital tract impairs fertility

MARTINEZ, MARIA SOL; FERREYRA, FERNANDO NICOLAS; PAIRA, DANIELA A.; OLIVERA, CAROLINA; RIVERO, VIRGINIA E.; MOTRICH, RUBEN D.

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAI&FAIC, SAFIS 2022; 2022

Urogenital inflammation has been proposed as a cause of male infertility as epidemiological studies revealed that it underlies at least 15% of male infertility cases. However, supporting evidence from animal models is scarce. Herein, we analyzed the development of Experimental Autoimmune Prostatitis (EAP) and its impact on fertility. C57BL/6 male mice were immunized with prostate antigens (PA) or saline on days 0 and 15. At day 24, males were mated with BALB/c female mice and different fertility parameters and uterine immune changes that occur after insemination were analyzed. Male mice were euthanized on day 26 and the specific immune response and prostate histopathology were assessed. Chronic pelvic pain development was evidenced by increased allodynia responses in PA-immunized male mice. Furthermore, significantly increased PA-specific lymphoproliferative responses with IFNg and IL17 secretion (p<0,0001) together with marked prostate periglandular macrophage and CD4+ T cell infiltration and tissue inflammatory lesions were observed. None of these changes were present in control mice. Interestingly, mating experiments revealed significantly decreased fertility indexes and augmented rates of pre- and post-implantation embryo loss in female mice mated with PA-immunized C57BL/6 males with respect to controls (p<0,05). Remarkably, these females showed alterations in the immune cell changes that physiologically occur in uterine mucosa after insemination such as significantly increased infiltration of macrophages, dendritic cells, NK cells and CD4+ T cells (p<0,05). Our results indicate that PA/specific Th1/Th17 immune responses underlie EAP associated chronic pelvic pain and prostate inflammation development. Of clinical interest, chronic inflammation of the prostate significantly impairs fertility by reducing the fertilizing ability of sperm, altering the uterine immune response triggered after insemination, and increasing embryo loss.