Mechanisms of fetal alcohol effects: role of acetaldehyde

Pregnant rats were treated from day 9 through 12 of gestation with 12.5% ethanol, 25% ethanol, 1% acetaldehyde, cyanamide (an inhibitor of the enzyme aldehyde dehydrogenase), or a combination of cyanamide and ethanol. Embryos were recovered on gestational day 12 and were quantitatively assessed on the basis of 16 recognizable developmental endpoints (morphological scores). The head and the crown-rump lengths of the embryos were also measured. Total resorption occurred in two animals treated with cyanamide and two treated with cyanamide and ethanol. Acetaldehyde and ethanol (at both concentrations) were found to reduce the head length of the embryos but had no significant effects on morphological scores and crown-rump length. The combination of ethanol with cyanamide caused a greater reduction in head length and also significantly reduced crown-rump length, as well as the morphological scores. The results suggest that the deleterious effects of ethanol could be attributed to acetaldehyde, its primary metabolite, although other underlying factors cannot be ruled out.