VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development
- University of Pennsylvania, United States
- University of South Florida, United States
Abstract
During formation of the mammalian placenta trophoblasts invade the maternal decidua and remodel spiral arteries to bring maternal blood into the placenta. This process, known as endovascular invasion, is thought to involve the adoption of functional characteristics of vascular endothelial cells (ECs) by trophoblasts. The genetic and molecular basis of endovascular invasion remains poorly defined, however, and whether trophoblasts utilize specialized endothelial proteins in an analogous manner to create vascular channels remains untested. Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of EC junctions. VE-cadherin is also expressed in invasive trophoblasts and is a prime candidate for a molecular mechanism of endovascular invasion by those cells. Here, we show that the VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua in the mouse. VE-cadherin deficiency results in loss of spiral artery remodeling that leads to decreased flow of maternal blood into the placenta, fetal growth restriction, and death. These studies identify a non-endothelial role for VE-cadherin in trophoblasts during placental development and suggest that endothelial proteins may play functionally unique roles in trophoblasts that do not simply mimic those in ECs.
Data availability
Source Data files have been included for Figure 1, Figure 1-Supplemental Figure 1, Figure 1-Supplemental Figure 2, Figure 1-Supplemental Figure 3, Figure 2, Figure 3, Figure 4-Supplemental Figure 1, and Figure 4-Supplemental Figure 2. All reagents have been listed in the Methods section in this paper.The RNA-seq data set has been deposited in the NCBI GEO under accession ID number GSE189408. Investigators interested in the animals used in this study should contact Dr. Jeremy Veenstra-Vanderweele (Columbia University), Dr. Gustsavo Leone (Medical University of South Carolina), and Dr. Joshua Scallan (University of South Florida).
Article and author information
Author details
Funding
National Institutes of Health (T32 HL007439)
- Derek C Sung
National Institutes of Health (F30 HL158014)
- Derek C Sung
American Heart Association (Postdoctoral Fellowship 35200213)
- Xiaowen Chen
National Institutes of Health (T32 HL007971)
- Thomas C Stevenson Keller
American Heart Association (Postdoctoral fellowship 836238)
- Thomas C Stevenson Keller
National Institutes of Health (HL142905)
- Joshua P Scallan
National Institutes of Health (HL145397)
- Ying Yang
National Institutes of Health (HL142976)
- Mark L Kahn
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were conducted using an approved animal protocol (806811) in accordance with the University of Pennsylvania Institutional Animal Care and Use Committee.
Copyright
© 2022, Sung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development
eLife 11:e77241.
https://doi.org/10.7554/eLife.77241
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