Fetal alcohol syndrome: cardiac birth defects in mice and prevention with folate

OBJECTIVE: Alcohol ( ethanol) consumption during pregnancy is linked to congenital heart defects that are associated with fetal alcohol syndrome. Recent reports have associated ethanol exposure with the Wnt/beta-catenin pathway. Therefore, we defined whether ethanol affects Wnt/beta-catenin signaling during cardiac cell specification. STUDY DESIGN: Pregnant mice on embryonic day 6.75 during gastrulation were exposed by an intraperitoneal injection to a binge-drinking dose of ethanol. Folic acid supplementation of mouse diet was tested for the prevention of ethanol-induced cardiac birth defects. RESULTS: Acute ethanol exposure induced myocardial wall changes and atrioventricular and semilunar valve defects, which was determined by echocardiography on embryonic day 15.5. A high folate diet prevented the ethanol-induced cardiac defects. Ethanol exposure in avian embryos suppressed 2 key Wnt-modulated genes that are involved in cardiac induction; folic acid rescued normal gene expression. CONCLUSION: Folic acid supplementation alone or with myoinositol prevented alcohol potentiation of Wnt/beta-catenin signaling that allowed normal gene activation and cardiogenesis.