Extracellular vesicles of first trimester trophoblast cell line overexpressing VPAC2 induce antiinflammatory signals in HB cell and maternal monocytes

PAPARINI, DANIEL E.; HAUK, VANESA C.; IZBIZKY, GUSTAVO; PÉREZ LEIRÓS, CLAUDIA; VOTA, DAIANA M.; LARA, BRENDA; RAMHORST, ROSANNA; GRASSO, ESTEBAN N.; MERECH, FÁTIMA; ABASOLO, JOSÉ IGNACIO

Bogotá

Congreso; IX SLIMP; 2022

SLIMP

Aims: Trophoblast cells release microvesicles and exosomes (Ex) that regulate target cell function at the early maternal-placental interface. We have previously shown the regulatory role of vasoactive intestinal peptide (VIP) and their VPAC receptors in human first trimester placenta and in trophoblast cell lines (Tb). Also, we reported that the overexpression of VPAC2 receptors in Tb increase cell migration and invasion. Here we studied the effect of extracellular microvesicles released by Tb overexpressing VPAC2 (Tb-VPAC2) on the phenotype and metabolism of human placental Hofbauer cells (HB) and circulating maternal monocytes (Mo).Methodology: Ex were characterized after isolation by differential centrifugation from Swan 71 cell line transfected with VPAC2 receptor or with empty vector (EV) as control. Peripheral blood Mo were obtained from normal pregnant women at term along with homologous HB cells from placental tissue by enzymatic digestion. HB and Mo were cultured with Ex to assess phenotypic profile, glucose uptake and lipid droplets formation by flow cytometryResults: Tb-VPAC2 secrete fewer small Ex (50 to 90 nm) and lower total Ex proteins than control cells. In contrast, no differences were observed in microvesicles secretion. Tb-VPAC2-Ex reduced CD40 production in CD14+/CD163+ HB vs. control Ex (*P