Antkiewicz Dagmara S, Burns C Geoffrey, Carney Sara A, Peterson Richard E, Heideman Warren
Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
Toxicol Sci. 2005 Apr;84(2):368-77. doi: 10.1093/toxsci/kfi073. Epub 2005 Jan 5.
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 h 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, one day prior to observable effects on peripheral blood flow. We conclude that the developing heart is an important target for TCDD in zebrafish.
斑马鱼（Danio rerio）已成为研究发育过程的一种有吸引力的脊椎动物模型，并且正逐渐成为研究有毒化合物扰乱正常发育机制的模型系统。受精后不久暴露于2,3,7,8-四氯二苯并对二恶英（TCDD）时，斑马鱼胚胎在受精后72小时（hpf）会出现心包水肿和血流减少。为了更好地了解二恶英在斑马鱼体内的毒性进展，我们研究了TCDD对心脏发育的影响。在72 hpf时，经TCDD处理的胚胎表现出心脏环化改变，心房明显位于心室后方，这与对照心脏的环化情况相反，对照心脏的两个腔室并排排列。此外，与对照组相比，暴露于二恶英的心脏中的心室变得更加紧实，心房拉长。这些缺陷并非心包水肿的继发结果，因为在通过渗透支持抑制水肿形成时也观察到了这些缺陷。除了形态学变化外，TCDD还使发育中的心脏产生功能缺陷，包括血液反流和明显的心室停搏，到120 hpf时这种情况变得很普遍。我们还使用体视学测量评估了TCDD对心脏大小的影响，结果表明在72 hpf时心脏组织体积显著减小。也许我们最显著的发现是，在对周边血流产生可观察到的影响前一天，即48 hpf时，暴露于TCDD的胚胎中心肌细胞总数减少。我们得出结论，发育中的心脏是斑马鱼体内TCDD的一个重要靶点。
