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9 February 2018 Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta
Sonia C. DaSilva-Arnold, Stacy Zamudio, Abdulla Al-Khan, Jesus Alvarez-Perez, Ciaran Mannion, Christopher Koenig, Davlyn Luke, Anisha M. Perez, Margaret Petroff, Manuel Alvarez, Nicholas P. Illsley
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Abstract

Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchoragedependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal–fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP). CTB and EVT were isolated from normal term placenta or placenta previa following Caesarean section and EVT from AIP following Caesarean hysterectomy. Cell identity was validated by measurement of cytokeratin-7 and HLA-G. Comparing normal term CTB with EVT from normal term placenta or placenta previa for differential expression analysis of genes associated with the EMT showed changes in >70% of the genes probed. While demonstrating a mesenchymal phenotype relative to CTB, many of the gene expression changes in third trimester EVT were reduced relative to the first trimester EVT. We suggest that third trimester EVT are in a more constrained, metastable state compared to first trimester equivalents. By contrast, EVT from AIP demonstrate characteristics that are more mesenchymal than normal third trimester EVT, placing them closer to first trimester EVT on the EMT spectrum, consistent with a more invasive phenotype.

Summary Sentence

Extravillous trophoblast cells from abnormally invasive placenta demonstrate more mesenchymal characteristics than normal third trimester cells, consistent with an overinvasive phenotype.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Sonia C. DaSilva-Arnold, Stacy Zamudio, Abdulla Al-Khan, Jesus Alvarez-Perez, Ciaran Mannion, Christopher Koenig, Davlyn Luke, Anisha M. Perez, Margaret Petroff, Manuel Alvarez, and Nicholas P. Illsley "Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta ," Biology of Reproduction 99(2), 409-421, (9 February 2018). https://doi.org/10.1093/biolre/ioy042
Received: 22 November 2017; Accepted: 7 February 2018; Published: 9 February 2018
JOURNAL ARTICLE
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