Trophoblast Giant Cell Profile And Immune Microenvironment Are Modulated By Endogenous VIP In Murine Implantation Sites

WASCHEK J; VOTA D, GRASSO E, RAMHORST R, ; HAUK V, CALO G, GALLINO L, ; PEREZ LEIROS C

Congreso; LXI Reunion Anual de la SAIC; 2016

Adequate trophoblast differentiation in an invasive phenotype is vital to ensure proper placentation. Among the factors that may facilitate trophoblast invasion are matrix metalloproteinases (MMP). Besides, trophoblast cells modulate leukocyte recruitment and function to maintain an anti-inflammatory andimmunosuppressant microenvironment. Vasoactive intestinal peptide (VIP) is a pleiotropic peptide with immunomodulatory effects through its action on VPAC1 and VPAC2 receptors. Using different murine models we have shown that VIP favors a suitable anti-inflammatory andimmunosuppressant profile for placentation and fetal growth. Moreover, we have found that VIP deficient pregnant mice have reduced litter size, increase the period inter-gestations and present an asymmetric distribution of implantation sites.Here we studied the relevance of endogenous VIP at the early maternal-placental interface and its impact on the local expression of immune and trophoblast functional markers in VIP KO mice.We isolated implantation sites from C57BL/6 WT mated to VIP-/- or WT males at day 8,5 of pregnancy and analyzed immune markers by RTqPCR, the percentage of Treg cells by flow cytometry or used laser capture microdissection (LCM) to isolate trophoblast giant cells (TGC) for the analysis of VPACs expression, MMP9 and TGC markers by RTqPCR.Implantation site explants from WT mothers crossed with VIP -/- males presented a reduced percentage of Foxp3-GFP+ Treg cells within CD4+ cells (X±ES: 10,3±1,7% WTxWT vs 5,2 ±1,3%WTxKO) and decreased IL-10 expression compared with WTxWT matings (P