Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Abstract

A successful pregnancy depends on the intricate and timely interactions of maternal and fetal cells. Placental extravillous cytotrophoblast invasion involves a cellular transition from an epithelial to mesenchymal phenotype. Villous cytotrophoblasts undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts and gain the capacity to migrate and invade. This review summarizes our current knowledge regarding known regulators of EMT in the human placenta, including the inducers of EMT, upstream transcription factors that control EMT and the downstream effectors, cell adhesion molecules and their differential expression and functions in pregnancy pathologies, preeclampsia (PE) and fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of the functional role of EMT targets in vitro. A better understanding of molecular pathways driven by placental EMT and further elucidation of signaling pathways underlying the developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in placental pathologies including PE and FGR.

P‐Glycoprotein (P‐gp)/ABCB1 plays a functional role in extravillous trophoblast (EVT) invasion and is decreased in the pre‐eclamptic placenta

“…EVT‐specific expression was maintained in invasive interstitial EVT throughout gestation and in differentiated individual cuboidal EVT at term. These data confirm, extend and validate our previous reports of P‐gp expression in these trophoblast subtypes . This is important considering that P‐gp is a critical component of the placental barrier and hence critical for a healthy pregnancy outcome, through its role in maintaining a balance of trophic factors.…”

“…These data confirm, extend and validate our previous reports of P-gp expression in these trophoblast subtypes. 11,19,32 This is important considering that P-gp is a critical component of the placental barrier and hence critical for a healthy pregnancy outcome, through its role in maintaining a balance of trophic factors. Notably, these data also further demonstrate a functional role for P-gp in EVT invasion.…”

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

“…In early placental development, cytotrophoblasts differentiate and lose their organized epithelial phenotype and transitioning to a more migratory and invasive mesenchymal phenotype which allows them to infiltrate the maternal decidua and spiral arteries. This transition has been recently suggested as a type of epithelial‐mesenchymal transition (EMT) that involves upregulating and secreting matrix metalloproteinase (MMP) and gaining the ability to migrate and invade . EMT has been reported to be mediated by tyrosine kinase receptors (TKR) and transforming growth factor beta family .…”

“…This transition has been recently suggested as a type of epithelial-mesenchymal transition (EMT) that involves upregulating and secreting matrix metalloproteinase (MMP) and gaining the ability to migrate and invade. [11][12][13][14][15] EMT has been reported to be mediated by tyrosine kinase receptors (TKR) and transforming growth factor beta family. [14][15][16] Among these receptors, TKR appears to have a direct and specific impact on endometrial susceptibility to implantation in vivo based on a murine TKR-ablated uterus model (epidermal growth factor receptor knockout).…”

Morphological Characterization of Basally Located Uninucleate Trophoblast Cells as Precursors of Bovine Binucleate Trophoblast Giant Cells

“…Downregulation of membrane-associated E-cadherin has been described as an event during epithelialmesenchymal transition (EMT) in other tissues [Morali et al, 2001;Yang and Liu, 2001]. EMT plays an important role in different biological processes, such as fetal development, tumor metastasis, and renal interstitial fibrosis [Yang and Liu, 2001;Thiery, 2002;Yang and Weinberg, 2008], as well as in the development of extravillous cytotrophoblast of the human placenta [Vicovac and Aplin, 1996;Davies et al, 2016]. Based on the above-mentioned findings of Nakano et al [2005], EMT might also play a role in the development of bovine TGCs.…”