Palmitic acid induces inflammation in placental trophoblasts and impairs their migration toward smooth muscle cells through plasminogen activator inhibitor-1.

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.

• Authors: Amanda M Rampersaud, Caroline E Dunk, Stephen J Lye, Stephen J Renaud
• Journal: Molecular human reproduction (Mol Hum Reprod) Vol. 26 Issue 11 Pg. 850-865 (11 01 2020) ISSN: 1460-2407 [Electronic] England
• PMID: 32898274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Inflammation Mediators
• Plasminogen Activator Inhibitor 1
• SERPINE1 protein, human
• Palmitic Acid

Topics

• Adult
• Cell Movement (drug effects, genetics)
• Cells, Cultured
• Decidua (drug effects, physiology)
• Female
• HEK293 Cells
• Humans
• Inflammation (blood, chemically induced, pathology, physiopathology)
• Inflammation Mediators (blood, pharmacology)
• Myocytes, Smooth Muscle (drug effects, physiology)
• Obesity (blood, complications, physiopathology)
• Palmitic Acid (blood, pharmacology)
• Placenta (cytology, drug effects)
• Placentation (drug effects, physiology)
• Plasminogen Activator Inhibitor 1 (blood, physiology)
• Pregnancy
• Pregnancy Complications (blood, physiopathology)
• Trophoblasts (cytology, drug effects, physiology)
• Young Adult