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. 2016 May 3;10(3):310-21.
doi: 10.1080/19336918.2016.1170258. Epub 2016 Apr 12.

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Jessica E Davies  1   2 , Jürgen Pollheimer  3 , Hannah E J Yong  1   2 , Maria I Kokkinos  2 , Bill Kalionis  1   2 , Martin Knöfler  3 , Padma Murthi  1   2   4
Affiliations

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Jessica E Davies et al. Cell Adh Migr. .

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.

Keywords: differentiation; epithelial-mesenchymal transition; invasion; placenta; trophoblast.

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Figures

Figure 1.
Figure 1.
Schematic diagram of trophoblast differentiation and invasion at the maternal-fetal interface. The boxed area is where EMT occurs at the anchoring villus cell column. Trophoblast cells differentiate from a proximal epithelial phenotype to a distal mesenchymal phenotype that is invasive. Figure adapted from Yamamoto-Tabata et al.
Figure 2.
Figure 2.
Color-coded mRNA expression patterns of regulated EMT-associated genes in non-invasive cyttrophoblasts referred to as “CTB” (n = 5) vs. differentiated EVTs (n = 6). Data (GDS3523) were analyzed by GEO DataSet Cluster Analysis online tool (http://www.ncbi.nlm.nih.gov/geo/). The upper panel represents expression pattern of CTB and EVTs markers to confirm purity of isolated cell pools. The middle and lower panels show up- and downregulated EMT-associated biomarkers in differentiated EVTs, respectively. CLDN, claudin; EGFR, epithelial growth factor receptor; FN1, fibronectin; FSP1, fibroblast-specific protein 1; HLA-G, human leucocyte antigen-G; HSP47, heat shock protein 47; ITGA, integrin α; ITGB1, integrin β 1; MMP2 matrix metalloproteinase 2; Notch2, notch drosophila homolog of 2; OCLN, occludin; MPP5, membrane protein palmitoylated 5; SPARC, secreted protein acid cysteine-rich; Snai1, snail1 drosophila homolog of 1; TCF4, T-cell transcription factor 4; ZO1, zona occludens 1 (Reproduced with permission from Knofler et al.18).
Figure 3.
Figure 3.
A schematic diagram describes the key regulatory transcription factors including TWIST, SNAIL, SIP1 and TCF involved in the EMT-like differentiation program of EVT, their downstream target genes, and the cross talk between different developmental signaling cascades, such as FGF, TGFβ and Wnt signaling cascade.
See this image and copyright information in PMC

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