Exposure to acrylamide disrupts cardiomyocyte interactions during ventricular morphogenesis in zebrafish embryos
Exposure to acrylamide disrupts cardiomyocyte interactions during ventricular morphogenesis in zebrafish embryos
复制标题
暴露于丙烯酰胺会破坏斑马鱼胚胎心室形态发生过程中心肌细胞的相互作用
DOI：
10.1016/j.scitotenv.2018.11.216
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发表时间：
2019
影响因子：
9.8
通讯作者：
Zhang Yu
中科院分区：
文献类型：
--
作者：
Huang Mengmeng;Zhu Fanghuan;Jiao Jingjing;Wang Jun;Zhang Yu
丙烯酰胺（AA）是一种无处不在的化学物质，存在于周围环境和烘焙或油炸富含碳水化合物的食物中，最近被认为与心脏发育毒性有关。然而，AA暴露在心脏发育中的毒理学作用在很大程度上仍然未知。在这里，我们展示了斑马鱼胚胎心室形态发生过程中AA的心脏毒性及其在心肌细胞相互作用中的作用。利用转基因斑马鱼胚胎模型tg (Tp1:d2GFP;myl7:mCherry)，我们发现AA在早期心脏发生过程中干扰了心内膜Notch信号的动态。长时间暴露于AA使室壁增厚，阻止小梁向室腔内延伸。结果，在心脏成熟过程中，AA通过过度激活心肌Notch信号，降低了心室缩短分数和空间维度。此外，暴露于AA抑制了n -钙粘蛋白的重新分布，由于缺乏分层的心肌细胞，无法协调心肌细胞在心肌层之间的相互作用。因此，aa处理的胚胎表现出亚细胞病理状态，包括肌原纤维紊乱和线粒体形态异常，尽管心肌细胞正常增殖。此外，我们发现与对照组相比，aa处理胚胎的心脏中一些心脏特异性转录因子如ashand2和nkx2.5过表达。本研究为斑马鱼室室形态发生时期可能是一个脆弱的窗口期提供了证据，并为AA如何发挥心脏发育毒性提供了新的见解。
Acrylamide (AA), a ubiquitous chemical that is present in surrounding environment and baked or fried carbohydrate-rich food, has recently been linked to cardiac developmental toxicity. However, the toxicological role of AA exposure in the cardiac development remains largely unknown. Here we showed the cardiotoxicity of AA and its role in cardiomyocyte interactions in zebrafish embryos during ventricular morphogenesis. Using the embryo model of transgenic zebrafishTg(Tp1:d2GFP;myl7:mCherry), we found AA interfered the dynamics of Notch signaling in the endocardium during early cardiogenesis. Prolonged exposure to AA thickened the chamber wall and prevented the trabeculae from extending into the lumen of ventricular chamber. As a result, AA reduced the ventricular shortening fraction and spatial dimension via excessively activating the Notch signal in myocardium during cardiac maturation. Moreover, exposure to AA inhibited the re-distribution ofN‑cadherin and failed to coordinate cardiomyocyte interactions between the myocardium layers due to the lack of delaminated cardiomyocytes. Therefore, AA-treated embryos exhibited subcellular pathological states including disarrayed myofibrils and abnormal morphology of mitochondria despite normal proliferation of cardiomyocytes. In addition, we found overexpression of some cardiac-specific transcription factors, such ashand2andnkx2.5, in hearts of AA-treated embryos compared with those in control group. Our study provided the evidence that the period of ventricular chamber morphogenesis might be a vulnerable window in zebrafish, and revealed new insights into how AA might exert cardiac developmental toxicity.