689 Maternal obesity is associated with lower circulating VEGF levels and reduced trophoblast cell migration

Abstract

Maternal obesity is known to be a significant contributing factor which increases the risk of developing prenatal complications. Our study aims to investigate the impact of maternal obesity on key circulating growth factors during gestation and growth factor-dependent invasive properties of placental trophoblast cells in vitro. We compared key growth factors and inflammatory cytokines in cord blood from 33 obese(BMI>30.0) and 45 non-obese(BMI=18.0-25.0) pregnant women at term C-section. Chemokine profiles were measured using EMD Millipore Luminex xMAP multiplex assays. Data acquisition was performed on Luminex200 and data analysis was done using xPONENT3.1. Invasive trans-migratory properties of HTR-8 placenta cells seeded on Matrigel and exposed to plasma from obese women were assessed by crystal violet and signal intensities were quantified using ImageJ. Invasion assays showed that trans-migratory properties of placental cells were significantly reduced when exposed to plasma from obese pregnant women compared to controls. Chemokine profiles revealed that maternal obesity caused a reduction in circulating VEGF levels. VEGF is known to be a key mediator of endothelial cell migration. Analysis of the VEGF interactome showed that VEGF physically interacts with ADAMTS1, a protease produced by visceral and subcutaneous adipose tissues, suggesting that obesity may lead to an increase in ADAM proteases and thus a higher degradation of their substrates including growth factors. Our findings support an original mechanistic model linking maternal obesity to an increased production of ADAMTS1 by fat tissue, triggering an abnormally high degradation of its natural substrates including growth factors such as VEGF, which would result in a reduction in trophoblast cell invasion. This could lead to the development of prenatal complications, including preeclampsia. Further work is needed to validate our findings and fully elucidate the mechanisms underlying the development of prenatal complications associated with maternal obesity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)