Embryonic ethanol exposure can cause fetal alcohol spectrum disorder (FASD) and, when severe, fetal alcohol syndrome (FAS). Symptoms include facial malformations, short stature and central nervous system defects. The mechanism responsible for the teratogenic effects of ethanol remains unknown, but one hypothesis proposes that ethanol competes with the enzymes that are needed to synthesize retinoic acid (RA), an important molecule in correct pattern formation during development. Using Xenopus embryos, Hadas Kot-Leibovich and Abraham Fainsod show that inhibition of one such enzyme, retinaldehyde dehydrogenase 2 (RALDH2), exaggerates ethanol-induced developmental defects, whereas increasing RALDH2 activity ameliorates the influence of ethanol exposure. This provides biochemical evidence that FASD and FAS abnormalities result from ethanol interference to normal RA synthesis during gastrulation.
