VIP deficiency promotes an inflammatory ovarian microenvironment impairing pregnancy

GALLINO L, HAUK V, MERECH F, GRASSO E, BESTACH Y, PASCUALI N, PARBORELL F, MAY M, FONTANA V, WASCHEK J, PEREZ LEIRÓS C, RAMHORST R

Congreso; Amereican Socitety of Reproductive Immunology meeting; 2021

Problem: Pregnancy is a unique process that needs to be finely orchaestrated to ensure a successful outcome. In particular, the immune system has a key role during every step from ovulation to delivery where, in normal conditions, cells and mediators interplay to protect the mother and the fetus. Vasoactive intestinal peptide (VIP) is a master regulatory peptide in the feto-maternal interface with antiinflammatory effects inducing a tolerogenic maternal response. Moreover, VIP regulates folliculogenesis and ovulation as well as ovarian steroidogenesis. As VIP KO mice are known to be subfertile, we aimed to better understand how VIP deficiency affects the development of normal pregnancy as regards ovarian physiology and immune homeostasis.Method of Study: Animal models: VIP Knockout KO (-/-), deficient HT (+/-) and wild type WT (+/+) mice in estrus (defined by vaginal lavage observation) were studied at 3 or 8 months of age. Serum hormones were measured with immulite Xpi Siemens platform. Ovaries were examined after histological staining, hormones quantified using RIA and IL-1β secretion by ELISA. The adoptive transfer of Regulatory T cells (Tregs) was performed with cells sorted by flow cytometry from Foxp3-knock-in-GFP females.Results: Young KO mice showed cycling disorders accompanied by an altered P4/E2 ratio in serum and ovary in the day of estrus as compared to WT mice of the same age. We also found histological differences between the ovaries, with an increase in secondary follicles, less corpora lutea, and more atretic follicles (p