title: Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid.
abstract: BACKGROUND
  Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known.
  
  
  RESULTS
  Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbs multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis, and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions.
  
  
  CONCLUSIONS
  Our results indicate that ethanol exposure interrupted divergent cardiac morphogenetic events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects.
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana.
authors.forename: Swapnalee
authors.initials: S
authors.lastname: Sarmah
authors.forename: James A
authors.initials: JA
authors.lastname: Marrs
mesh_terms: D020751:Alcohol-Induced Disorders / Q000196:embryology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005492:Folic Acid / Q000494:pharmacology*; D054262:Gastrulation / Q000187:drug effects; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000196:embryology / Q000473:pathology / Q000517:prevention & control*; D038081:Organogenesis / Q000187:drug effects; D014803:Vitamin B Complex / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D002492:Central Nervous System Depressants; D014803:Vitamin B Complex; D000431:Ethanol; D005492:Folic Acid
keywords: cardiac defects; congenital heart defects; ethanol exposure; fetal alcohol spectrum disorder; zebrafish