Zebrafish fetal alcohol syndrome model: effects of ethanol are rescued by retinoic acid supplement

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2010-11, Vol.44 (7), p.707-715
• Main Authors: Marrs, James A, Clendenon, Sherry G, Ratcliffe, Don R, Fielding, Stephen M, Liu, Qin, Bosron, William F
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - prevention & control; Acids; Animals; Biosynthesis; Cell adhesion & migration; Disease Models, Animal; Embryo, Nonmammalian; Embryogenesis; Embryonic Development - drug effects; Embryos; Ethanol; Ethanol - administration & dosage; Ethanol - toxicity; Evacuations & rescues; Experiments; Female; Fetal Alcohol Spectrum Disorders - prevention & control; Fetal alcohol syndrome; Gastrulation; Psychiatry; Retinoic acid; Software; Somitogenesis; Tretinoin - administration & dosage; Zebrafish; Zebrafish - embryology
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2009.03.004

Abstract This study was designed to develop a zebrafish experimental model to examine defects in retinoic acid (RA) signaling caused by embryonic ethanol exposure. RA deficiency may be a causative factor leading to a spectrum of birth defects classified as fetal alcohol spectrum disorder (FASD). Experimental support for this hypothesis using Xenopus showed that effects of treatment with ethanol could be partially rescued by adding retinoids during ethanol treatment. Previous studies show that treating zebrafish embryos during gastrulation and somitogenesis stages with a pathophysiological concentration of ethanol (100 mM) produces effects that are characteristic features of FASD. We found that treating zebrafish embryos with RA at a low concentration (10−9 M) and 100 mM ethanol during gastrulation and somitogenesis stages significantly rescued a spectrum of defects produced by treating embryos with 100 mM ethanol alone. The rescued phenotype that we observed was quantitatively more similar to embryos treated with 10−9 M RA alone (RA toxicity) than to untreated or 100 mM ethanol-treated embryos. RA rescued defects caused by 100 mM ethanol treatment during gastrulation and somitogenesis stages that include early gastrulation cell movements (anterior–posterior axis), craniofacial cartilage formation, and ear development. Morphological evidence also suggests that other characteristic features of FASD (e.g., neural axis patterning) are rescued by RA supplement.