Ethanol disrupts the formation of hypochord and dorsal aorta during the development of embryonic zebrafish |
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Authors: | Qian Linxi Wang Yuexiang Jiang Qiu Zhong Tao Song Houyan |
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Institution: | Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical School of Fudan University, Shanghai 200032, China. |
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Abstract: | Exposure to ethanol during human embryonic period has severe teratogenic effects on the cardiovascular system. In our study, we demonstrated that ethanol of gradient concentra-tions can interfere with the establishment of circulatory system in embryonic zebrafish. The ef-fective concentration to cause 50% malformations (EC50) was 182.5 mmol/L. The ethanol pulse exposure experiment displayed that dome stage during embryogenesis is the sensitive time window to ethanol. It is found that 400 mmol/L ethanol pulse exposure can induce circulatory defects in 43% treated embryos. We ruled out the possibility that ethanol can interfere with the process of hematopoiesis in zebrafish. By employing in situ hybridization with endothelial bio-marker (Flk-1), we revealed that ethanol disrupts the establishment of trunk axial vasculature, but has no effect on cranial vessels. Combined with the results of semi-thin histological sections, the in situ hybridization experiments with arterial and venous biomarkers (ephrinB2, ephB4) sug-gested that ethanol mainly interrupts the development of dorsal aorta while has little effect on axial vein. Further study indicated the negative influence of ethanol on the development of hy-pochord in zebrafish. The consequent lack of vasculogenic factors including Radar and Ang-1 partly explains the defects in formation and integrity of dorsal aorta. These results provide im-portant clues to the study of adverse effects of ethanol on the cardiovascular development in human fetus. |
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Keywords: | Ethanol zebrafish dorsal aorta hypochord vasculogenesis |
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