ToxSci Advance Access published online on January 5, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi073
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1 Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705, USA
* To whom correspondence should be addressed. The zebrafish (Danio rerio) has become an attractive vertebrate model for studying developmental processes, and is emerging as a model system for studying the mechanisms by which toxic compounds perturb normal development. When exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) shortly after fertilization, zebrafish embryos exhibit pericardial edema and reduced blood flow by 72 hours post fertilization (hpf). To better understand the progression of dioxin toxicity in zebrafish, we have examined the effects of TCDD on heart development. At 72 hpf, TCDD-treated embryos exhibited altered looping, with the atria positioned distinctly posterior to the ventricles, contrary to the looping of control hearts, where the two chambers lied side by side. Moreover, the ventricles in dioxin-exposed hearts became more compact, and the atria elongated in comparison to controls. These defects are not secondary to pericardial edema because they were observed when edema formation was suppressed with osmotic support. In addition to morphological changes, TCDD produced functional deficits in the developing hearts, including blood regurgitation and a striking ventricular standstill that became prevalent by 120 hpf. We also assessed the effect of TCDD on the heart size using stereological measurements, which demonstrated significant reduction in heart tissue volume at 72 hpf. Perhaps our most significant finding was a decrease in the total number of cardiomyocytes in TCDD-exposed embryos by 48 hpf, 1 day prior to observable effects on peripheral blood flow. We conclude that the developing heart is an important target for TCDD in zebrafish.
Received October 29, 2004
Accepted December 22, 2004
Reproductive and Developmental Toxicology
Heart Malformation is an Early Response to TCDD in Embryonic Zebrafish
2 Developmental Biology Laboratory, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
3 Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705, USA; School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, USA
Warren Heideman, E-mail: wheidema{at}facstaff.wisc.edu
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