Structural and functional effects of developmental exposure to ethanol on the zebrafish heart.
BACKGROUND
Fetal alcohol exposure during development results in a host of cardiac abnormalities including atrial and ventricular septal defects, teratology of Fallot, d-transposition of the great arteries, truncus arteriosus communis, and aortico-pulmonary window. The mechanisms behind these ethanol-induced deficits are unknown. The purpose of this study was to determine whether the zebrafish, a simple model in which heart development and the sequence of gene expression is well elucidated and comparable to that in higher vertebrates, is sensitive to developmental exposure of pharmacologically relevant concentrations of ethanol.


METHODS
Zebrafish eggs of the AB strain were raised in egg water or in 0.5% (v/v) ethanol solution for either 54 hpf (hours postfertilization) or 72 hpf. Heart pathology and volumes were evaluated on the latter group at 5 dpf (days postfertilization) on tissue sections from fixed larvae embedded in glycolmethacrylate. Heart rates were determined in embryos of 54 hpf and larvae of 5 dpf. The functional maturity of the heart's conducting system was measured by determining the response of ethanol-treated and control embryos and larvae to the adrenergic agonist, isoproterenol, and the cholinergic agonist, carbachol.


RESULTS
Ethanol-induced alterations occurred in heart morphology and heart volume. A developmental lag in the isoproterenol response and the absence of carbachol-mediated bradycardia were also observed following ethanol treatment.


CONCLUSIONS
These results show that exposure of the zebrafish to ethanol during development results in structural and functional changes in the heart that mimic malformations that occur in patients with fetal alcohol syndrome (FAS). These findings promote the zebrafish heart as a future model for investigating the mechanisms responsible for ethanol's adverse effects on vertebrate heart development.
Dlugos
Cynthia A
CA
Department of Pathology and Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA. cadlugos@buffalo.edu
Rabin
Richard A
RA
D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002306:Cardiac Volume / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000196:embryology* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D023421:Models, Animal; D015027:Zebrafish
D000322:Adrenergic Agonists; D002492:Central Nervous System Depressants; D018679:Cholinergic Agonists; D000431:Ethanol; D002217:Carbachol; D007545:Isoproterenol