Palmitic acid induces inflammation in placental trophoblasts and impairs their migration toward smooth muscle cells through plasminogen activator inhibitor-1. (8th September 2020)

• Record Type: Journal Article
• Authors: Rampersaud, Amanda M; Dunk, Caroline E; Lye, Stephen J; Renaud, Stephen J
• Is Part Of: Molecular human reproduction. Volume 26:Number 11(2020)
• Page Start: 850
• Page End: 865
• Publication Date: 2020-09-08
• Subjects: extravillous trophoblasts -- smooth muscle cells -- obesity -- palmitic acid -- plasminogen activator inhibitor-1 -- cell migration; Human reproduction -- Molecular aspects -- Periodicals; Electronic journals; 612.6
• DOI: 10.1093/molehr/gaaa061
• Languages: English
• ISSNs: 1360-9947

Abstract

Abstract: A critical component of early human placental development includes migration of extravillous trophoblasts (EVTs) into the decidua. EVTs migrate toward and displace vascular smooth muscle cells (SMCs) surrounding several uterine structures, including spiral arteries. Shallow trophoblast invasion features in several pregnancy complications including preeclampsia. Maternal obesity is a risk factor for placental dysfunction, suggesting that factors within an obese environment may impair early placental development. Herein, we tested the hypothesis that palmitic acid, a saturated fatty acid circulating at high levels in obese women, induces an inflammatory response in EVTs that hinders their capacity to migrate toward SMCs. We found that SMCs and SMC-conditioned media stimulated migration and invasion of an EVT-like cell line, HTR8/SVneo. Palmitic acid impaired EVT migration and invasion toward SMCs, and induced expression of several vasoactive and inflammatory mediators in EVTs, including endothelin, interleukin (IL)-6, IL-8 and PAI1. PAI1 was increased in plasma of women with early-onset preeclampsia, and PAI1-deficient EVTs were protected from the anti-migratory effects of palmitic acid. Using first trimester placental explants, palmitic acid exposure decreased EVT invasion through Matrigel. Our findings reveal that palmitic acid induces an inflammatory response in EVTs and attenuates their migration through a mechanism involving PAI1. High levels of palmitic acid in pathophysiological situations like obesity may impair early placental development and predispose to placental dysfunction.