Vascular endothelial growth factor receptors 1 and 3 mediate placental trophoblast leptin production in preeclampsia, inducing vascular dysfunction

The receptors for VEGF and PlGF, membrane-bound VEGFR, are expressed in placental trophoblast cells, but their functions in this cell type are largely unknown. Placenta production of leptin significantly increases in preeclampsia, and we recently showed leptin induces placental and vascular endothelial dysfunction in pregnancy.

We hypothesized that inappropriately high sFlt-1 in preeclampsia leads to an increase in trophoblast leptin production. We treated human placental explants, trophoblast and adipose cells with sFlt-1 and show an increase in leptin peptide production, which is ablated by coadministration with either VEGF or placental growth factor (PlGF). We further demonstrate that VEGFR1 and 3, not R2, expressions are predominant in human trophoblasts and that reducing activation of these receptors mediates trophoblast leptin production.