Chronic Inflammation Of The Male Genital Tract Impairs Female Genital Tract Immunomodulation and Decreases Fertility Potential

Cape Town

Congreso; 18th International Congress of Immunology ? IUIS2023; 2023

International Union of Immunology Societies

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.The aim of this study is to assess the role of chronic prostatitis as a possible cause of male infertility, evaluating the consequences of inflammation in semen on its normal ability to modulate the immune response in the female genital tract, promote uterine remodeling and embryo implantation.C57BL/6 male mice were immunized with prostate antigens (PA) or saline (C) on days 0 and 15 and the specific immune response, prostate histopathology and infiltrating leukocytes were assessed on day 26. At day 24, males were mated with BALB/c female mice and uterine immune changes that occur after insemination and different fertility parameters were analyzed. Chronic pelvic pain development was evidenced by increased allodynia responses in PA-immunized male mice. Furthermore, they showed significantly increased PA-specific lymphoproliferative responses with IFNγ and IL17 secretion (p<0,0001) together with marked prostate periglandular macrophage and CD4+ T cell infiltration (p<0,001) and tissue inflammatory lesions. Interestingly, female mice mated with PA-immunized showed significantly decreased fertility indexes and elevated rates of pre- and post-implantation embryo loss with respect to controls (p<0,05). Remarkably, after 8 hours of copulation, these females showed increased infiltrates of macrophages, dendritic cells, NK cells and CD4+ T cells in the uterine mucosa than controls (p<0,05). Additionally, at the peri-implantation period, they showed increased infiltration of effector CD4+ T cells, macrophages, dendritic cells and NK cells (p<0,05).Our results indicate that PA-specific Th1/Th17 immune responses underlie the development of chronic prostatitis and pelvic pain. Of clinical interest, chronic prostatitis significantly impairs fertility by reducing the fertilizing ability of sperm, altering the uterine immune response triggered after insemination, and increasing embryo loss.