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/β-catenin pathway. Therefore, we defined whether ethanol affects Wnt/β-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/β-catenin signaling that allowed normal gene activation and cardiogenesis. 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/β-catenin pathway. Therefore, we defined whether ethanol affects Wnt/β-catenin signaling during cardiac cell specification. 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. 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. Folic acid supplementation alone or with myoinositol prevented alcohol potentiation of Wnt/β-catenin signaling that allowed normal gene activation and cardiogenesis.