Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia. Academic Article uri icon

Overview

MeSH

  • Adult
  • Animals
  • Case-Control Studies
  • Cell Lineage
  • Disease Models, Animal
  • Down-Regulation
  • Endothelial Cells
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Placentation
  • Pregnancy
  • RNA, Messenger
  • Receptors, Notch
  • Signal Transduction
  • Trophoblasts

MeSH Major

  • Endothelial Growth Factors
  • Placenta
  • Pre-Eclampsia
  • Proteins

abstract

  • The mammalian placenta is the site of nutrient and gas exchange between the mother and fetus, and is comprised of two principal cell types, trophoblasts and endothelial cells. Proper placental development requires invasion and differentiation of trophoblast cells, together with coordinated fetal vasculogenesis and maternal vascular remodeling. Disruption in these processes can result in placental pathologies such as preeclampsia (PE), a disease characterized by late gestational hypertension and proteinuria. Epidermal Growth Factor Like Domain 7 (EGFL7) is a largely endothelial-restricted secreted factor that is critical for embryonic vascular development, and functions by modulating the Notch signaling pathway. However, the role of EGFL7 in placental development remains unknown. In this study, we use mouse models and human placentas to begin to understand the role of EGFL7 during normal and pathological placentation. We show that Egfl7 is expressed by the endothelium of both the maternal and fetal vasculature throughout placental development. Importantly, we uncovered a previously unknown site of EGFL7 expression in the trophoblast cell lineage, including the trophectoderm, trophoblast stem cells, and placental trophoblasts. Our results demonstrate significantly reduced Egfl7 expression in human PE placentas, concurrent with a downregulation of Notch target genes. Moreover, using the BPH/5 mouse model of PE, we show that the downregulation of Egfl7 in compromised placentas occurs prior to the onset of characteristic maternal signs of PE. Together, our results implicate Egfl7 as a possible factor in normal placental development and in the etiology of PE. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

publication date

  • August 2014

has subject area

  • Adult
  • Animals
  • Case-Control Studies
  • Cell Lineage
  • Disease Models, Animal
  • Down-Regulation
  • Endothelial Cells
  • Endothelial Growth Factors
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Placenta
  • Placentation
  • Pre-Eclampsia
  • Pregnancy
  • Proteins
  • RNA, Messenger
  • Receptors, Notch
  • Signal Transduction
  • Trophoblasts

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4177412

Digital Object Identifier (DOI)

  • 10.1016/j.mod.2014.04.001

PubMed ID

  • 24751645

Additional Document Info

start page

  • 163

end page

  • 176

volume

  • 133