VIP deficiency disrupts immune ovarian homeostasis.

S GORI, L CASTAGNOLA, L GALLINO, D VOTA, E GRASSO, F PARBORELL, C PÉREZ LEIRÓS, V HAUK AND R RAMHORST.

Chicago

Congreso; American Association of Immunologists; 2024

American Association of Immunologists

AAI registration: 4318VIP deficiency disrupts immune ovarian homeostasis María Soledad Gori1, Lara Castagnola1, Lucila Gallino1, Daiana Vota1, Esteban Grasso1, , Fernanda Parborell2, Claudia Pérez Leirós1, Vanesa Hauk1 and Rosanna Ramhorst11 IQUIBICEN, University of Buenos Aires, CONICET, Argentina.2 Estudios de la Fisiopatología del ovario, IBYME, CONICET, Argentina.Ovarian aging is associated with inflammation, contributing to the decline in oocyte count and quality. Since the vasoactive intestinal peptide (VIP) is an immunopeptide found in the reproductive tract with anti inflammatory effects inducing a tolerogenic response, we focus on VIP contribution to ovarian immune homeostasis preventing premature aging. We observed that young VIP KO mice (3 months old) display an altered ovarian histology with an increase in atretic follicles and less mature follicles as in aged WT mice (8 months old). This microenvironment was accompanied by an increased fibrosis deposition, ROS and IL-1β production. Interestingly, we found a significant decrease in ovarian reserve and the presence of foamy macrophages in young VIP KO ovary associated with premature aging. Getting insight into the mechanism involved in foam cell generation, we pre-conditioned young WT or VIP KO macrophages with WT or VIP KO ovarian media for 48h to mimic the ovarian microenvironment. Macrophages from VIP KO mice display a differential phagocytic ability of apoptotic bodies after preconditioning with WT or VIP KO ovarian media. However, only in VIP KO macrophages conditioned with VIP KO ovarian media we found an increase in lipid droplet accumulation, consistent with the formation of foamy macrophages. These findings highlight the role of VIP in regulating ovarian immune microenvironment, thereby preserving ovarian health and preventing premature aging.