title: The yolk sac theory: closing the circle on why diabetes-associated malformations occur.
abstract: OBJECTIVE
  The purpose of this article is to examine the role of yolk sac failure during organogenesis in the development of diabetes-associated embryopathy.
  
  
  METHODS
  The current literature regarding congenital malformations in diabetic pregnancies was reviewed to elucidate the precise role of the yolk sac in embryonic development and the relation between yolk sac injury and embryopathy.
  
  
  RESULTS
  We and others have demonstrated that hyperglycemia produces a teratogenic effect during organogenesis. In addition, we have shown that the yolk sac appears to be the target site of injury induced by hyperglycemia. We have also presented evidence that cell membrane dysfunction leads to failed vitelline vessel formation and that arachidonic acid supplementation prevents many of the morphologic and biochemical alterations observed under hyperglycemic conditions.
  
  
  CONCLUSIONS
  These data strongly support the teratogenic effect of hyperglycemia, the arachidonic acid deficiency state, the resultant maldevelopment of vitelline vessels, and the ability to prevent these changes by arachidonic acid supplementation. These studies have made significant inroads in explaining why diabetes-associated anomalies occur, and suggest a potential future role for prophylaxis against these organogenetic malformations using dietary polyunsaturated fatty acid supplementation.
authors.affiliation: Department of Obstetrics and Gynecology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Reece
authors.forename: E
authors.initials: E
authors.lastname: Pinter
authors.forename: C
authors.initials: C
authors.lastname: Homko
authors.forename: Y K
authors.initials: YK
authors.lastname: Wu
authors.forename: F
authors.initials: F
authors.lastname: Naftolin
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology* / Q000503:physiopathology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic; D015017:Yolk Sac / Q000473:pathology*
chemical_list: D005231:Fatty Acids, Unsaturated