Human trophoblast cell migration and invasion are induced by endogenous vasoactive intestinal peptide (VIP) through autocrine circuits and VPAC2 overexpression

DAIANA VOTA; VANESA HAUK; AYELEN TORO; ESTEBAN GRASSO; DANIEL PAPARINI; ROSANNA RAMHORST; CECILIA VARONE; CLAUDIA PÉREZ LEIRÓS

Mar del Plata

Congreso; Latin American Symposium on Maternal Fetal Interaction & Placenta; 2015

The generation of the human maternal-placental interface requirestrophoblast differentiation into phenotypes able to migrate and invade thedeciduas. VIP is a pleiotropic polypeptide with immunomodulatory effectsthrough VPAC1 and VPAC2 receptors. Previously, we have reported on itsimmune homeostasis maintenance role at early pregnancy. The expressionof VIP in various cell types is induced by growth factors or neurotransmittersand 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; HTR-8) and its impact on trophoblast cellmigration and invasion.Methods: VIP expression was measured by flow cytometry and RT-qPCR;cell migration was determined by wound healing assays and invasivenessin Matrigel-covered transwells. Trophoblast cells were transfected with XtremeGENE HPDNA reagent with VPAC2 or CRE-Luciferase plasmids for24h prior to the stimuli, normalized to GFP or beta-gal.Results: Endogenous VIP expression was detected in trophoblast cells andits synthesis was induced after 18 h incubation with 10nM VIP (P