Ethanol disrupts the formation of hypochord and dorsal aorta during the development of embryonic zebrafish.
Exposure to ethanol during human embryonic period has severe teratogenic effects on the cardiovascular system. In our study, we demonstrated that ethanol of gradient concentrations can interfere with the establishment of circulatory system in embryonic zebrafish. The effective 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 biomarker (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) suggested 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 hypochord 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 important clues to the study of adverse effects of ethanol on the cardiovascular development in human fetus.
Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical School of Fudan University, Shanghai 200032, China.
Linxi
L
Qian
Yuexiang
Y
Wang
Qiu
Q
Jiang
Tao
T
Zhong
Houyan
H
Song
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000196:embryology; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D050982:GATA1 Transcription Factor / Q000032:analysis / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D017403:In Situ Hybridization / Q000379:methods; D023421:Models, Animal; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism; D014680:Veins / Q000196:embryology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000032:analysis / Q000378:metabolism
D050982:GATA1 Transcription Factor; D013723:Teratogens; D029961:Zebrafish Proteins; C494691:gata1a protein, zebrafish; D000431:Ethanol; D040301:Vascular Endothelial Growth Factor Receptor-2