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.


METHODS
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.


CONCLUSIONS
Folic acid supplementation alone or with myoinositol prevented alcohol potentiation of Wnt/beta-catenin signaling that allowed normal gene activation and cardiogenesis.
Serrano
Maria
M
Pediatric Residency Program, College of Medicine, University of Florida, Jacksonville, FL, USA.
Han
Mingda
M
Brinez
Pilar
P
Linask
Kersti K
KK
D000818:Animals; D002642:Chick Embryo; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D005492:Folic Acid / Q000494:pharmacology*; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000196:embryology / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011897:Random Allocation; D018608:Ultrasonography, Doppler; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism
D051153:Wnt Proteins; D051176:beta Catenin; D000431:Ethanol; D005492:Folic Acid