Experimental fetal alcohol syndrome: proposed pathogenic basis for a variety of associated facial and brain anomalies.

Acute teratogenic exposure of C57Bl/6J mouse embryos to ethanol in vivo results, within 12 hours of initial insult, in excessive cell death in selected cell populations. The patterns of excessive cell death observed following exposure of gestational day 8 embryos (late presomite--approximately 5 somite pair stages) vary somewhat temporospatially, but primarily involve the cell populations at the rim of the anterior neural plate. The cell death patterns appear to be pathogenically correlated with subsequently observed malformations including exencephaly (anencephaly), arhinencephaly, pituitary dysplasia, bilateral or unilateral cleft lip, maxillary hypoplasia, and median facial deficiencies and clefts. The association of these brain and facial malformations in this model, and perhaps in humans, may be accounted for by early insult to the selected cell populations identified in the current investigation.