Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis mimicking features of human intrauterine growth restriction.

Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulateplacental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to confirm the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2-/- ) were generated. These animals are fertile but have reduced litter sizes. Moreover, their placentas exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Emp2-/- animals have reduced HIF-1α expression within cells of trophoblast origin. However, they appear to have a compensatory increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1a expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in conditions of altered oxygen availability in mice and humans and suggest it may be a novel biomarker for placental insufficiency.

Dataset features

Information

Specifications

Application:	RNA-seq analysis
Number of samples:	6
Release date:	Feb 23 2017
Last update date:	Nov 26 2018
Access:	Public
Diseases:	Placental Insufficiency, Corneal Neovascularization
Chemicals:	Oxygen
Dataset link	Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis mimicking features of human intrauterine growth restriction.

Experimental Protocol

Day 13.5 placental tissue was isolated from Emp2+/+ and Emp2-/- animals and snap-frozen. Total RNA from each tissue was extracted using theRNAeasy kit (Qiagen. 3 samples per group were subjected to Illumina sequencing using the UCLA Pathology and Laboratory Medicine Core. Libraries for RNA-seq were prepared with KAPA Stranded RNA-Seq Kit.

Repositories

GEO

GSE81940

ENA

SRP075761

BioProject

PRJNA323469

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Contact

Madhuri Wadehra