The molecular mechanism of fetal alcohol syndrome (FAS). I. Ethanol-induced growth suppression.
Of the birth defects associated with alcohol consumption during pregnancy, in situ growth retardation resulting in neonates that are small for gestational age is the most common observation in both humans and animal models. A variety of alcohol-induced alterations in maternal, placental and/or fetal physiology have been proposed as the basis for this retarded fetal growth. The molecular mechanism(s) of this retardation, however, is obscure; and it remains to be determined whether the growth suppression is the result of the action of ethanol or its metabolites on embryonic, maternal or placental tissue. Using the embryonic chick as a model which circumvents changes in maternal and placental function, we have measured ethanol-induced growth suppression as a function of embryonic age and ethanol dosage. The data suggest that ethanol per se suppresses the rate of cell division in embryonic tissue resulting in fewer cells/embryo for a given time of gestation. The suppression of cell division is proportional to the ethanol dose and appears to be related to ethanol-induced changes in the metabolism of the prostaglandin hormones and resulting changes in the cyclic-AMP levels of the developing embryos.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001827:Body Height / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000201:enzymology*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism
D011453:Prostaglandins; D000431:Ethanol; D004247:DNA; D000242:Cyclic AMP; D000429:Alcohol Oxidoreductases; D006911:Hydroxyprostaglandin Dehydrogenases; D000426:Alcohol Dehydrogenase