Hypoxia and the Edema Syndrome: elucidation of a mechanism of teratogenesis.
The elucidation of mechanisms and pathogenesis of birth defects is exceedingly complex. Consequently, there are few examples where the etiology of birth defects caused by a specific agent has been well described. One such example is the "Edema Syndrome" first described by Casimer Grabowski in the 1960s as a mechanism of hypoxia-induced malformations in the chick embryo. The Edema Syndrome comprised a series of events in the embryo starting with osmotic imbalances followed by edema, distention, blisters, hematomas, and hemorrhage in or near developing structures. Malformation or deformation of structures resulted from mechanical disruption or loss of blood supply. A similar etiology has since been described by others in a variety of laboratory mammals following treatment with drugs including epinephrine, hydroxyurea, cocaine, phenytoin, and potassium channel-blocking drugs. Free radical excess following transient hypoxia may be a common factor in all of these insults. Vascular disruption is also associated with a number of birth defects in humans, including limb and digit reduction defects and urogenital defects.
Chernoff
Neil
N
Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Rogers
John M
JM
D000014:Abnormalities, Drug-Induced / Q000196:embryology*; D000818:Animals; D001768:Blister / Q000139:chemically induced / Q000196:embryology; D002642:Chick Embryo; D003042:Cocaine / Q000009:adverse effects; D004487:Edema / Q000196:embryology*; D004837:Epinephrine / Q000009:adverse effects; D006406:Hematoma / Q000139:chemically induced / Q000196:embryology; D006470:Hemorrhage / Q000139:chemically induced / Q000196:embryology; D006918:Hydroxyurea / Q000009:adverse effects; D000860:Hypoxia / Q000139:chemically induced / Q000196:embryology*; D010672:Phenytoin / Q000009:adverse effects; D026902:Potassium Channel Blockers / Q000009:adverse effects; D013577:Syndrome
D026902:Potassium Channel Blockers; D010672:Phenytoin; D003042:Cocaine; D006918:Hydroxyurea; D004837:Epinephrine