Heart malformation is an early response to TCDD in embryonic zebrafish
Heart malformation is an early response to TCDD in embryonic zebrafish
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DOI：
10.1093/toxsci/kfi073
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Heideman, W
中科院分区：
文献类型：
--
作者：
Antkiewicz, DS;Burns, CG;Heideman, W
斑马鱼（Danio rerio）已经成为研究发育过程的有吸引力的脊椎动物模型，并且正在成为研究有毒化合物扰乱正常发育的机制的模型系统。当受精后不久暴露于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 h（hpf）表现出心包水肿和血流减少。为了更好地了解斑马鱼二恶英毒性的进展，我们研究了TCDD对心脏发育的影响。在72 hpf，TCDD处理的胚胎表现出改变循环，与心房定位明显落后于心室，相反的循环控制心脏，其中两个腔室并排。此外，与对照组相比，暴露于二恶英的心脏的心室变得更加紧凑，心房延长。这些缺陷不是继发于心包水肿，因为它们是在渗透支持抑制水肿形成时观察到的。除了形态学的变化，TCDD在发育中的心脏中产生功能缺陷，包括血液反流和在120 hpf时变得普遍的显著心室停顿。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少。也许我们最重要的发现是TCDD暴露的胚胎中心肌细胞总数减少了48 hpf，在外周血流量观察到影响的前一天。我们的结论是，发育中的心脏是一个重要的目标TCDD在斑马鱼。
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.