Chronic inflammation of the male genital tract impairs male fertility. Results from an animal model

MARTINEZ, MARIA SOL; FERREYRA, FERNANDO NICOLAS; PAIRA, DANIELA A.; MOTRICH, RUBEN D.

Varadero

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

Background: urogenital inflammation is a putative cause of male infertility. Indeed, epidemiological studies have revealed that male urogenital inflammation underlies at least 15% of male infertility cases. However, available supporting evidence from animal models is very scarce. Aim: as our laboratory has pioneered the development of Experimental Autoimmune Prostatitis rodent models, which have reflected most human disease features, we herein analyzed its development and impact on male fertility potential. C57BL/6 male mice were immunized with prostate antigens (PA) or saline (C) plus adjuvant on days 0 and 15. Pelvic pain induction was assayed as tactile allodynia using Von Frey filaments. At day 24, mating experiments with BALB/c female mice were performed and different fertility parameters analyzed. Animals were euthanized on day 26 and the specific immune response, prostate histopathology and infiltrating leukocytes analyzed. Results: chronic pelvic pain development was evidenced by increased allodynia responses in the pelvic region of PA-immunized mice. Furthermore, these animals showed significantly increased PA-specific lymphoproliferative responses with IFNg and IL17 secretion together with marked prostate periglandular infiltration and tissue inflammatory changes. Infiltrates were mainly composed of CD4+ T cells and macrophages. Also, PA-immunized mice showed significantly elevated serum levels of PA-specific IgG autoantibodies. On the contrary, none of these changes were observed in control mice. Interestingly, mating experiments revealed a significant decrease in the fertility index and augmented percentages of pre- and post-implantation embryo loss in BALB/c female mice mated with PA-immunized C57BL/6 mice with respect to females mated with controls. Conclusions: Our results indicate that Th1/Th17 associated immune responses develop and induce chronic pelvic pain and prostate inflammation and after PA immunization of C57BL/6 mice. In turn, prostate inflammation significantly impairs male fertility potential by reducing the fertilizing ability of sperm and increasing the rate of embryo loss.