MicroRNAs and Fetal Brain Development: Implications for Ethanol Teratology during the Second Trimester Period of Neurogenesis.
MicroRNAs and Fetal Brain Development: Implications for Ethanol Teratology during the Second Trimester Period of Neurogenesis.
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DOI：
10.3389/fgene.2012.00077
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发表时间：
2012
影响因子：
3.7
通讯作者：
Miranda RC
中科院分区：
文献类型：
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作者：
Miranda RC
母亲在怀孕期间的酒精消费可导致胎儿颅面、心血管、骨骼和神经缺陷的刻板集群，统称为胎儿酒精谱系障碍（FASD）。胎儿酒精暴露是智力迟钝的主要非遗传原因。乙醇致畸的病因机制是多种多样的，复杂的。这篇评论将集中在发展中的大脑作为一个重要的和脆弱的乙醇目标。在前三个月结束时和第二个三个月期间，胎儿神经干细胞（NSC）产生成人大脑的大部分神经元，乙醇已被证明会影响NSC的更新和成熟。我们将讨论microRNA（miRNAs）的生物发生和功能的神经发育和致畸影响，miRNAs是一类通过翻译抑制控制基因网络表达的非蛋白质编码小RNA。一个小但不断增长的研究机构已经确定了NSC和大脑成熟的不同阶段的乙醇敏感性miRNA。虽然许多miRNAs在特定的发育阶段似乎对乙醇敏感，但少数miRNAs，如miR-9家族，似乎在NSC分化的多个阶段对乙醇表现出广泛的敏感性。对这些miRNAs的调节和功能的评估提供了有关胎儿对母胎环境改变的脆弱性机制的重要线索，并对FASD的发生产生了深刻的见解。
Maternal ethanol consumption during pregnancy can lead to a stereotypic cluster of fetal craniofacial, cardiovascular, skeletal, and neurological deficits that are collectively termed the fetal alcohol spectrum disorder (FASD). Fetal ethanol exposure is a leading non-genetic cause of mental retardation. Mechanisms underlying the etiology of ethanol teratology are varied and complex. This review will focus on the developing brain as an important and vulnerable ethanol target. Near the end of the first trimester, and during the second trimester, fetal neural stem cells (NSCs) produce most of the neurons of the adult brain, and ethanol has been shown to influence NSC renewal and maturation. We will discuss the neural developmental and teratological implications of the biogenesis and function of microRNAs (miRNAs), a class of small non-protein-coding RNAs that control the expression of gene networks by translation repression. A small but growing body of research has identified ethanol-sensitive miRNAs at different stages of NSC and brain maturation. While many miRNAs appear to be vulnerable to ethanol at specific developmental stages, a few, like the miR-9 family, appear to exhibit broad vulnerability to ethanol across multiple stages of NSC differentiation. An assessment of the regulation and function of these miRNAs provides important clues about the mechanisms that underlie fetal vulnerability to alterations in the maternal-fetal environment and yields insights into the genesis of FASD.