GLYCOLYSIS AND OXIDATIVE PHOSPHORYLATION ARE NECESSARY FOR VASOACTIVE INTESTINAL PEPTIDE-MEDIATED MIGRATION IN TROHPOBLAST CELLS

F MERECH; B LARA; D RIOS; V HAUK; D PAPARINI; G CALO; M VIDELA ; M GARCIA; M CHEMEN; R RAMHORST; ME MONGE; C PÉREZ LEIRÓS; D VOTA

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Trophoblast cells display different functional phenotypes to support placental development and fetal growth. Extravillous cytotrophoblast cells (EVT) acquire a migratory and invasive phenotype, regulate immune responses and vascular transformation maintaining placental homeostasis. A highly active metabolism of trophoblast cells is required to attend the dynamic demands of the placenta and fetus throughout pregnancy but how EVT integrate metabolic signals remains unclear. We have previously shown that vasoactive intestinal peptide (VIP) stimulates cytotrophoblast cell glucose and amino acid metabolism in vitro and in vivo, as well as it promotes cell migration in vitro.Our goal was to deepen into the metabolic pathways activated upon VIP stimulation of EVT, their role in cell migration and VIP effect on TCA and glycolysis metabolites accumulation. The human EVT-like cell line Swan-71 was cultured with VIP (10-100 nM). Cell migration was evaluated by wound healing assay using 2-DG or Rotenone as glycolysis and electron transport chain inhibitors. Lactate, pyruvate, succinate and other metabolites were assessed by Accutrend Plus System or semi-targeted metabolomic approaches. Long chain fatty acids (LCFAs) uptake and lipid droplets were analyzed by flow cytometry with BODIPY-FL C12 and 493/503 fluorescent probes. Expression of LCFAs transporters FATP1/2/4, metabolic regulator PPARg and lactate transporters MCT1/4 by RT-qPCR. VIP promoted EVT migration via glycolysis and oxidative phosphorylation (*p