Fainsod Abraham, Kot-Leibovich Hadas
Department of Cellular Biochemistry and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Biochem Cell Biol. 2018 Apr;96(2):77-87. doi: 10.1139/bcb-2017-0219. Epub 2017 Oct 25.
Vertebrate model systems are central to characterize the outcomes of ethanol exposure and the etiology of fetal alcohol spectrum disorder (FASD), taking advantage of their genetic and morphological closeness and similarity to humans. We discuss the contribution of amphibian embryos to FASD research, focusing on Xenopus embryos. The Xenopus experimental system is characterized by external development and accessibility throughout embryogenesis, large clutch sizes, gene and protein activity manipulation, transgenesis and genome editing, convenient chemical treatment, explants and conjugates, and many other experimental approaches. Taking advantage of these methods, many insights regarding FASD have been obtained. These studies characterized the malformations induced by ethanol including quantitative analysis of craniofacial malformations, induction of fetal growth restriction, delay in gut maturation, and defects in the differentiation of the neural crest. Mechanistic, biochemical, and molecular studies in Xenopus embryos identified early gastrula as the high alcohol sensitivity window, targeting the embryonic organizer and inducing a delay in gastrulation movements. Frog embryos have also served to demonstrate the involvement of reduced retinoic acid production and an increase in reactive oxygen species in FASD. Amphibian embryos have helped pave the way for our mechanistic, molecular, and biochemical understanding of the etiology and pathophysiology of FASD.
脊椎动物模型系统对于表征乙醇暴露的结果以及胎儿酒精谱系障碍（FASD）的病因至关重要，这得益于它们在遗传和形态上与人类的相近性和相似性。我们讨论两栖动物胚胎对FASD研究的贡献，重点是非洲爪蟾胚胎。非洲爪蟾实验系统的特点包括整个胚胎发育过程中的体外发育和易操作性、大量的卵块、基因和蛋白质活性操纵、转基因和基因组编辑、便捷的化学处理、外植体和结合物以及许多其他实验方法。利用这些方法，已经获得了许多关于FASD的见解。这些研究表征了乙醇诱导的畸形，包括颅面畸形的定量分析、胎儿生长受限的诱导、肠道成熟延迟以及神经嵴分化缺陷。对非洲爪蟾胚胎进行的机制、生化和分子研究确定原肠胚早期是高酒精敏感性窗口，靶向胚胎组织者并导致原肠胚形成运动延迟。蛙胚胎也已用于证明视黄酸产生减少和活性氧增加与FASD有关。两栖动物胚胎有助于为我们对FASD病因和病理生理学的机制、分子和生化理解铺平道路。
