Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid.
Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid.
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DOI：
10.1002/dvdy.24015
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发表时间：
2013-10
影响因子：
2.5
通讯作者：
Marrs, James A.
中科院分区：
文献类型：
--
作者：
Sarmah, Swapnalee;Marrs, James A.
关键词：
胎儿酒精谱系障碍（FASD）描述了一系列出生缺陷，包括各种先天性心脏缺陷（CHD）。FASD相关CHD的机制尚不清楚。酒精是否会干扰心脏形成中的单个关键事件或多个事件尚不清楚。我们的斑马鱼胚胎实验表明，乙醇中断了不同的心脏调节网络，扰乱了心脏发生的多个步骤（规格，心肌迁移，循环，腔室形态发生和内膜垫形成）。乙醇暴露在原肠胚形成期间，直到心脏规格或心肌中线迁移过程中没有产生严重或持续的心脏发育缺陷。然而，包括原肠胚形成直至心肌前体中线融合或在心脏模式化阶段期间的暴露产生了异常的心脏循环和有缺陷的内膜垫。在整个心脏发生过程中持续暴露会产生复杂的心脏缺陷，导致严重缺陷的心肌、内皮细胞和内皮细胞垫。维甲酸与乙醇的补充部分挽救了早期心脏发育缺陷，但内膜垫没有正确形成。相反，补充叶酸可以挽救正常的心脏发育，包括内膜垫。我们的研究结果表明，乙醇暴露中断了导致心脏缺陷的不同心脏形态发生事件。补充叶酸可有效预防酒精引起的广泛心脏发育缺陷。
Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects.
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影响因子：
2.7
作者：
Blader, P;Strähle, U
通讯作者：
Strähle, U
影响因子：
2.9
作者：
ABEL, EL
通讯作者：
ABEL, EL
影响因子：
4.6
作者：
Hochgreb, T;Linhares, VL;Xavier-Neto, J
通讯作者：
Xavier-Neto, J
DOI：
10.1136/bmj.b1673
发表时间：
2009-05-12
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Ionescu-Ittu R;Marelli AJ;Mackie AS;Pilote L
通讯作者：
Pilote L
影响因子：
3.7
作者：
Hutson JR;Stade B;Lehotay DC;Collier CP;Kapur BM
通讯作者：
Kapur BM