Retinoic-acid-induced limb malformations resulting from apical ectodermal ridge cell death.
Retinoic-acid-induced limb malformations resulting from apical ectodermal ridge cell death.
复制标题
视黄酸诱导的顶端外胚层嵴细胞死亡导致的肢体畸形。
DOI：
10.1002/tera.1420370602
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Dehart,DB
中科院分区：
文献类型：
--
作者：
Sulik,KK;Dehart,DB
受精后 9 天 12 小时，妊娠 C57B1/6J 小鼠单次口服剂量为 400 mg/kg 的 13-顺式视黄酸（RA、异维A酸、Accutane）芝麻油。在 10 名接受治疗的母亲的 16 天活胎儿中，46% (26/56) 患有肢体畸形，包括小第五指、轴前和/或轴后少指，以及轴前或轴后多指。轴前手指缺陷的胎儿也有半径缺失或畸形。对导致这些畸形的发育改变序列的扫描电子显微镜和光学显微镜分析表明，顶端外胚层脊（AER）存在异常。 27-30 个体节胚胎（治疗后 12 小时）AER 中的过度细胞死亡似乎在观察到的肢体畸形的发病机制中发挥着重要作用。之前对类维生素A引起的肢体畸形的研究主要集中在较晚的暴露时间上。这项研究的证据加上之前的畸形学和临床研究的证据得出了这样的假设：13-cis RA 导致程序性细胞死亡区域的细胞过度死亡以及受影响区域随后的畸形。
Pregnant C57B1/6J mice were treated with single oral doses of 400 mg/kg 13‐cis retinoic acid (RA, isotretinoin, Accutane) in sesame oil at 9 days, 12 hours postfertilization. Among the live 16‐day fetuses from ten treated mothers, 46% (26/56) had limb malformations including small fifth digits, preaxial and/or postaxial oligodactyly, and preaxial or postaxial polydactyly. Fetuses with preaxial digit deficiencies also had absent or malformed radii. Scanning electron microscopic and light microscopic analyses of the sequence of developmental alterations leading to these malformations demonstrated abnormalities in the apical ectodermal ridge (AER). Excessive cell death in the AER of 27–30 somite enbryos (12 hours after treatment) appears to play a major role in the pathogenesis of the limb malformations observed. Previous investigations of retinoid‐induced limb malformations have concentrated on later exposure times. Evidence from this study in addition to that from previous teratologic and clinical investigations has led to the hypothesis that 13‐cis RA results in excessive cell death in regions of programmed cell death and subsequent malformations of affected regions.