Extravillous trophoblast migration and invasion: Impact of environmental chemicals and pharmaceuticals

Reprod Toxicol. 2022 Jan;107:60-68. doi: 10.1016/j.reprotox.2021.11.008. Epub 2021 Nov 25.

Abstract

During pregnancy, the migration and invasion of extravillous trophoblasts (EVTs) into the maternal uterus is essential for proper development of the placenta and fetus. During the first trimester, EVTs engraft and remodel maternal spiral arteries allowing for efficient blood flow and the transfer of essential nutrients and oxygen to the fetus. Aberrant migration of EVTs leading to either shallow or deep invasion into the uterus has been implicated in a number of gestational pathologies including preeclampsia, fetal growth restriction, and placenta accreta spectrum. The migration and invasion of EVTs is well-coordinated to ensure proper placentation. However, recent data point to the ability of xenobiotics to disrupt EVT migration. These xenobiotics include heavy metals, endocrine disrupting chemicals, and organic contaminants and have often been associated with adverse pregnancy outcomes. In most instances, xenobiotics appear to reduce EVT migration; however, there are select examples of enhanced motility after chemical exposure. In this review, we provide an overview of the 1) current experimental approaches used to evaluate EVT migration and invasion in vitro, 2) ability of environmental chemicals and pharmaceuticals to enhance or retard EVT motility, and 3) signaling pathways responsible for altered EVT migration that are sensitive to disruption by xenobiotics.

Keywords: Extravillous trophoblast; Migration; Placenta; Placenta accreta spectrum; Preeclampsia; Pregnancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Drug-Related Side Effects and Adverse Reactions*
  • Environmental Pollutants / toxicity*
  • Humans
  • Trophoblasts / drug effects*
  • Trophoblasts / physiology
  • Xenobiotics / toxicity*

Substances

  • Environmental Pollutants
  • Xenobiotics