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Exposure to acrylamide disrupts cardiomyocyte interactions during ventricular morphogenesis in zebrafish embryos

Author:
Huang, Mengmeng, Zhu, Fanghuan, Jiao, Jingjing, Wang, Jun, Zhang, Yu
Source:
The Science of the total environment 2019 v.656 pp. 1337-1345
ISSN:
0048-9697
Subject:
Danio rerio, acrylamides, cadherins, cardiotoxicity, developmental toxicity, embryo (animal), gene overexpression, genetically modified organisms, mitochondria, models, morphogenesis, myofibrils, transcription factors
Abstract:
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 zebrafish Tg(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 of N‑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 as hand2 and nkx2.5, 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.
Agid:
6232858