HUMAN TROPHOBLAST CELL MIGRATION AND INVASION ARE INDUCED BY ENDOGENOUS VASOACTIVE INTESTINAL PEPTIDE (VIP) THROUGH AUTOCRINE CIRCUITS AND VPAC2 OVEREXPRESSION

VOTA D ; HAUK V; TORO A; GRASSO E; PAPARINI D; RAMHORST R; VARONE C; PEREZ LEIROS C

Congreso; VI SLIMP|V LASRI Meeting Maternal-Fetal Interaction; 2015

The generation of the human maternal-placental interface requires trophoblast differentiation into phenotypes able to migrate and invade the deciduas. VIP is a pleiotropic polypeptide with immunomodulatory effects through VPAC1 and VPAC2 receptors and we reported on its immune homeostasis maintenance role at early pregnancy. The expression of VIP in various cell types is induced by growth factors or neurotransmitters and depends on CRE (cAMP responsive elements) and gp130 cytokine (CyRE) sites on its promoter. Objective: To investigate VIP/VPAC2 expression on first trimester cytotrophoblast cells (Swan-71 and HTR-8) and its impact on trophoblast cell migration and invasion.Material and Methods: VIP expression was measured by flow cytometry and RT-qPCR; cell migration by wound healing assays and invasiveness in Matrigel-covered transwells. Trophoblast cells were transfected with X-tremeGENE HPDNA reagent with VPAC2 or CRE-Luciferase plasmids for 24h prior to the stimuli, normalized to GFP or b-gal. Results: Endogenous VIP expression was detected in Swan71 and HTR8 cell lines and its synthesis was induced after 18 h incubation with 10nM VIP (P