Fainsod Abraham, Bendelac-Kapon Liat, Shabtai Yehuda
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, POB 12271, 9112102, Jerusalem, Israel.
Subcell Biochem. 2020;95:197-225. doi: 10.1007/978-3-030-42282-0_8.
Fetal Alcohol Spectrum Disorder (FASD) is a complex set of developmental malformations, neurobehavioral anomalies and mental disabilities induced by exposing human embryos to alcohol during fetal development. Several experimental models and a series of developmental and biochemical approaches have established a strong link between FASD and reduced retinoic acid (RA) signaling. RA signaling is involved in the regulation of numerous developmental decisions from patterning of the anterior-posterior axis, starting at gastrulation, to the differentiation of specific cell types within developing organs, to adult tissue homeostasis. Being such an important regulatory signal during embryonic development, mutations or environmental perturbations that affect the level, timing or location of the RA signal can induce multiple and severe developmental malformations. The evidence connecting human syndromes to reduced RA signaling is presented here and the resulting phenotypes are compared to FASD. Available data suggest that competition between ethanol clearance and RA biosynthesis is a major etiological component in FASD.
胎儿酒精谱系障碍（FASD）是一组复杂的发育畸形、神经行为异常和智力残疾，由人类胚胎在胎儿发育期间暴露于酒精引起。多种实验模型以及一系列发育和生化方法已经在FASD与视黄酸（RA）信号传导减弱之间建立了紧密联系。RA信号传导参与从原肠胚形成开始的前后轴模式形成，到发育器官内特定细胞类型的分化，再到成体组织稳态等众多发育决策的调控。作为胚胎发育过程中如此重要的调节信号，影响RA信号水平、时间或位置的突变或环境干扰可诱发多种严重的发育畸形。本文展示了将人类综合征与RA信号传导减弱联系起来的证据，并将由此产生的表型与FASD进行了比较。现有数据表明，乙醇清除与RA生物合成之间的竞争是FASD的一个主要病因成分。
