Fetal alcohol syndrome and DiGeorge anomaly: critical ethanol exposure periods for craniofacial malformations as illustrated in an animal model.
Fetal alcohol syndrome and DiGeorge anomaly: critical ethanol exposure periods for craniofacial malformations as illustrated in an animal model.
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胎儿酒精综合症和迪乔治异常：动物模型中所示的颅面畸形的关键乙醇暴露期。
DOI：
10.1002/ajmg.1320250614
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发表时间：
1986
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;Johnston,MC;Daft,PA;Russell,WE;Dehart,DB
急性母体乙醇（酒精）管理诱导不同的颅面畸形的后代的实验动物，这取决于妊娠日致畸暴露。我们实验室以前的研究已经说明了导致“典型”胎儿酒精综合征（FAS）颅面表型的发育变化的顺序，该表型是原肠胚形成期间致畸剂暴露的结果。这些面部特征伴随着正中前脑衍生物的缺陷。此时乙醇致畸作用明显导致胚胎椎间盘中线区域的丧失，对神经嵴依赖性侧向衍生结构（包括内脏弓）的影响很小。小鼠急性乙醇暴露1天半后，此时神经嵴细胞正在填充额鼻突和内脏弓，导致颅面表型与DiGeorge异常或序列中观察到的相似。在我们的实验室中，对暴露于第8天半的胚胎进行的连续扫描电子显微镜分析表明，发育中的面部神经和内脏弓存在缺陷。发育中的前脑和中脑发育不全。我们还观察到这些胎儿的心脏、大血管和胸腺异常。组织学分析表明，上述（第8天半诱导）胎儿酒精效应的共同发病基础似乎是对颅（包括枕）神经嵴完整性的干扰。其他离散的细胞群也可能参与，因为我们已经观察到异常的其他地区，包括基板和封闭膜tissues.This动物模型提供的证据，喜欢母亲酒精滥用在第3或第4周的himan妊娠FAS或DiGeorge异常颅面特征的发展，分别在孕体。由于DiGeorge异常已经在酗酒女性的后代中被注意到，该动物模型表明，在这些情况下，乙醇和/或其代谢物是致病因子。
Acute maternal ethanl (alcohol) administration induces different craniofacial anomalies in the offspring of experimental animals, depending on the gestational day of teratogen exposure. Previous studies in our laboratories have illustrated the sequence of developmental changes leading to the “typical” fetal alcohol syndrome (FAS) craniofacial phenotype which results from teratogen exposure during gastrulation. These facial features are accompanied by deficiencies in median forebrain derivatives. Ethanol teratogenesis at this time apparently results in a loss of midline territory of the embryonic disc with little effect on neural crest‐dependent laterally derived structures including the visceral arches. Acute ethanol exposure in mice 1 ½ days later, at a time when neural crest cells are populating the frontonasal prominence and the visceral arches, results in a craniofacial phenotype that is similar to that noted in the DiGeorge anomaly or sequence. Sequential scanning electron microscopic analysis in our laboratory of embryos exposed on day 8 ½ have illustrated deficiencies in the developing facial prominences and the visceral arches. The developing forebrain and midbrain appear hypoplastic. We have also observed heart, great vessel, and thymus abnormalities in these fetuses. Histologic analyses indicate that a common pathogenetic basis for the above‐mentioned (day 8 ½‐induced) fetal alcohol effects appears to be an interference with the integrity of the cranial (including occipital) neural crest. Other discrete cell populations may also be involved since we have observed abnormalities in other regions, including placodal and closing membrane tissues.This animal model provides evidence liking maternal ethanol abuse during the 3rd or 4th weeks of himan gestation to the development in the conceptus of FAS or DiGeorge anomally craniofacial characteristics, respectively. As the DiGeorge anomaly has been noted in the offspring of alcoholic women, this animal model indicates that ethanol and/or its metabolities is, in these cases, the causative agent.