The mechanism by which ethanol produces its teratogenic effects have included abnormal prostaglandin metabolism, chromosomal alterations, placental dysfunction, hypoxia, interference with protein synthesis, altered growth signaling, interference with neurotransmitter production which can lead to neuroendocrine abnormalities, and alteration of enzymes which regulate glycogen synthesis and degradation. Retinoic acid, a vitamin A derivative, has been shown to play an important role in the specification of spatial patterns during the morphogenesis of the nervous system and limbs as well as a role in epithelial cell differentiation. Retinoic acid is considered a morphogen and believed to help establish the anteroposterior axis of both the nervous system and limbs. During ontogeny, retinoic acid probably regulates events that mediate the transcription of genes that control nervous system and limb morphogenesis. An alteration in the synthesis of this molecule may produce adverse effects on the developing organism.
Ethanol regulates such a disruption in retinoic acid synthesis and result in teratogenic effects.
Ethanol competitively inhibits the alcohol dehydrogenase transformation of retinal or vitamin A into retinal. The conversion of retinol to retinal by this enzyme is believed to be the rate limiting step in the production of retinoic acid. Retinol dehydrogenase is considered equivalent to class 1 ADH in man. In intoxication states, class 1 ADH is saturated with ethanol. Thus, retinol oxidation is blocked.