Early Development of the Primordial Mammalian Diaphragm and Cellular Mechanisms of Nitrofen-Induced Congenital Diaphragmatic Hernia
Early Development of the Primordial Mammalian Diaphragm and Cellular Mechanisms of Nitrofen-Induced Congenital Diaphragmatic Hernia
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DOI：
10.1002/bdra.20613
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Greer, John J.
中科院分区：
文献类型：
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作者：
Clugston, Robin D.;Zhang, Wei;Greer, John J.
先天性横隔疝(CDH)是新生儿呼吸窘迫的常见原因，具有较高的死亡率和长期的发病率。来自动物模型的证据表明，CDH起源于胸膜腹膜皱折畸形(PPF)，PPF是胚胎横隔膜形成的关键结构。本研究的目的是研究PPF在大鼠和人类中的胚胎发生特点，并确定导致CDH硝芬模型PPF发育异常的潜在机制。对大鼠胚胎和存档的人类胚胎切片的分析，可以确定这两个物种的PPF形成的时间框架，从而描绘出与CDH相关的横隔膜发育的关键时期。在体外对暴露于硝苯醚的NIH3T3细胞进行的实验使我们推测，硝苯芬可能通过两种可能的机制在体内引起横隔疝：通过抑制细胞增殖或通过诱导细胞凋亡。来自暴露于硝苯醚的大鼠胚胎的数据表明，硝苯醚在PPF中致畸的主要机制是通过减少细胞增殖。本研究为大鼠和人PPF的胚胎发生提供了新的视角，并提示细胞增殖受损可能是CDH硝化芬模型中横隔膜发育异常的原因之一。出生缺陷研究(A部分)88：15-24,2010。(C)2009年Wiley-Liss，Inc.
Congenital diaphragmatic hernia (CDH) is a frequently occurring cause of neonatal respiratory distress and is associated with high mortality and long-term morbidity. Evidence from animal models suggests that CDH has its origins in the malformation of the pleuroperitoneal fold (PPF), a key structure in embryonic diaphragm formation. The aims of this study were to characterize the embryogenesis of the PPF in rats and humans, and to determine the potential mechanism that leads to abnormal PPF development in the nitrofen model of CDH. Analysis of rat embryos, and archived human embryo sections, allowed the timeframe of PPF formation to be determined for both species, thus delineating a critical period of diaphragm development in relation to CDH. Experiments on nitrofen-exposed NIH 3T3 cells in vitro led us to hypothesize that nitrofen might cause diaphragmatic hernia in vivo by two possible mechanisms: through decreased cell proliferation or by inducing apoptosis. Data from nitrofen-exposed rat embryos indicates that the primary mechanism of nitrofen teratogenesis in the PPF is through decreased cell proliferation. This study provides novel insight into the embryogenesis of the PPF in rats and humans, and it indicates that impaired cell proliferation might contribute to abnormal diaphragm development in the nitrofen model of CDH. Birth Defects Research (Part A) 88:15-24, 2010. (C) 2009 Wiley-Liss, Inc.