Altered feto-placental vascularization, feto-placental malperfusion and fetal growth restriction in mice with Egfl7 loss of function

Development. 2017 Jul 1;144(13):2469-2479. doi: 10.1242/dev.147025. Epub 2017 May 19.


EGFL7 is a secreted angiogenic factor produced by embryonic endothelial cells. To understand its role in placental development, we established a novel Egfl7 knockout mouse. The mutant mice have gross defects in chorioallantoic branching morphogenesis and placental vascular patterning. Microangiography and 3D imaging revealed patchy perfusion of Egfl7-/- placentas marked by impeded blood conductance through sites of narrowed vessels. Consistent with poor feto-placental perfusion, Egfl7 knockout resulted in reduced placental weight and fetal growth restriction. The placentas also showed abnormal fetal vessel patterning and over 50% reduction in fetal blood space. In vitro, placental endothelial cells were deficient in migration, cord formation and sprouting. Expression of genes involved in branching morphogenesis, Gcm1, Syna and Synb, and in patterning of the extracellular matrix, Mmrn1, were temporally dysregulated in the placentas. Egfl7 knockout did not affect expression of the microRNA embedded within intron 7. Collectively, these data reveal that Egfl7 is crucial for placental vascularization and embryonic growth, and may provide insight into etiological factors underlying placental pathologies associated with intrauterine growth restriction, which is a significant cause of infant morbidity and mortality.

Keywords: Branching morphogenesis; Egfl7; Endothelial dysfunction; Gcm1; Mmrn1; Placenta.

MeSH terms

  • Animals
  • Base Sequence
  • Blood Proteins / genetics
  • Blood Proteins / metabolism
  • Body Patterning
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Movement
  • Down-Regulation / genetics
  • EGF Family of Proteins
  • Endothelial Cells / metabolism
  • Female
  • Fetal Blood / metabolism
  • Fetal Growth Retardation / metabolism*
  • Fetal Growth Retardation / pathology*
  • Fetus / embryology
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Physiologic*
  • Organ Size
  • Perfusion*
  • Placenta / blood supply*
  • Placenta / embryology*
  • Placenta / metabolism
  • Placentation*
  • Pregnancy
  • Proteins / metabolism*


  • Blood Proteins
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • EGF Family of Proteins
  • Egfl7 protein, mouse
  • Mmrn1 protein, mouse
  • Proteins