Creech Kraft J, Kimelman D, Juchau M R
Department of Pharmacology, University of Washington, Seattle 98195.
Drug Metab Dispos. 1995 Jan;23(1):83-9.
This study demonstrates early embryonic metabolism of exogenous all-trans-3,4-didehydroretinol (vitamin A2) to all-trans-3,4-didehydroretinal and to all-trans-3,4-didehydroretinoic acid in Xenopus embryos during neurulation. The latter metabolite was recently shown to bind with high affinity and to activate various retinoic acid receptors. Embryos treated with all-trans-3,4-didehydroretinol during early or late gastrulation exhibited abnormalities along the anteroposterior axis. The abnormalities were primarily in the posterior regions of the embryo, with only minor defects anteriorally. Eye malformations, typical for early exposure to 9-cis- and all-trans-retinols and retinals (companion paper), were not observed. We also present evidence that all-trans-3,4-didehydroretinoic acid is present endogenously during early neurulation and is evenly distributed along the anteroposterior axis. After treatment with all-trans-3,4-didehydroretinol, embryonic levels of all-trans-3,4-didehydroretinoic acid exceeded endogenous levels of this metabolite during early and late neurulation. We hypothesize that the dysmorphogenic effects produced by treatment of Xenopus embryos with the alcohol precursor, all-trans-3,4-didehydroretinol, are the result of its embryonic conversion to its corresponding acid ligand.
本研究表明，在非洲爪蟾胚胎神经胚形成期间，外源性全反式-3,4-二脱氢视黄醇（维生素A2）在胚胎早期代谢为全反式-3,4-二脱氢视黄醛和全反式-3,4-二脱氢视黄酸。最近发现，后一种代谢产物能以高亲和力结合并激活各种视黄酸受体。在原肠胚形成早期或晚期用全反式-3,4-二脱氢视黄醇处理的胚胎沿前后轴出现异常。异常主要出现在胚胎的后部区域，前部只有轻微缺陷。未观察到早期暴露于9-顺式和全反式视黄醇及视黄醛时典型的眼部畸形（相关论文）。我们还提供证据表明，全反式-3,4-二脱氢视黄酸在神经胚形成早期内源性存在，并沿前后轴均匀分布。用全反式-3,4-二脱氢视黄醇处理后，在神经胚形成早期和晚期，胚胎中全反式-3,4-二脱氢视黄酸的水平超过了该代谢产物的内源性水平。我们推测，用醇前体全反式-3,4-二脱氢视黄醇处理非洲爪蟾胚胎所产生的致畸作用是其胚胎转化为相应酸性配体的结果。
