Maternal diabetes: effects on embryonic vascular development--a vascular endothelial growth factor-A-mediated process.
Major congenital malformations, many of which result from abnormal cardiovascular patterning, remain the leading cause in infant mortality and morbidity. Targeted mutations of several genes (including VEGF and VEGF receptors) and certain teratogenic agents (including excess alpha-D-glucose) give rise to embryonic lethal phenotypes associated with failure in the formation of a functional vitelline circulation and aberrant organogenesis. Our work to date has demonstrated that yolk sac vasculopathy and failure of endocardial cushion epithelial-mesenchymal transformation occurs in hyperglycemic conditions in murine whole conceptus culture and in embryos from streptozotocin-induced diabetic mice. These cardiovascular abnormalities are associated with changes in expression and phosphorylation state of adhesion molecules such as platelet endothelial growth factor-1 and expression of growth factors such as vascular endothelial growth factor (VEGF-A). Further understanding of the effects of maternal diabetes on yolk sac and embryonic vasculogenesis/angiogenesis and organogenesis may lead to novel approaches in treating and preventing major birth defects.
Madri
Joseph A
JA
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, P.O. Box 208023, New Haven, CT 06520-8023, USA. joseph.madri@yale.edu
Enciso
Josephine
J
Pinter
Emese
E
D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002196:Capillaries / Q000196:embryology; D003921:Diabetes Mellitus, Experimental; D005314:Embryonic and Fetal Development; D004699:Endocardium / Q000196:embryology; D005260:Female; D006943:Hyperglycemia / Q000196:embryology; D051379:Mice; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014817:Vitelline Membrane / Q000098:blood supply
D042461:Vascular Endothelial Growth Factor A