Goulding E H, Jetten A M, Abbott B D, Pratt R M
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Reprod Toxicol. 1988;2(2):91-8. doi: 10.1016/0890-6238(88)90003-2.
Isotretinoin (13-cis-RA) is a human teratogen and mouse embryos exposed to 13-cis-RA in vivo exhibit many of the same defects as humans. Early postimplantation mouse embryos exposed to 13-cis-RA in culture exhibit developmental alterations of the visceral arches, similar to those seen after in vivo exposure. Certain benzoic acid derivatives of retinoic acid have been shown to possess activity equal to or greater than retinoic acid in several in vitro systems. This study examines the teratogenic effects of some of these retinoids on mouse embryos in vitro. Day 8 CD-1 mouse embryos were cultured for 48 hours in the presence of these benzoic acid derivatives. With the exception of Ro-15-0778, all compounds produced visceral arch malformations similar to those seen in embryos exposed to 13-cis-RA, but at dramatically different effective concentrations. Extremely low concentrations of the retinoic acid-related compounds tested appear to have detrimental effects on embryonic development and these compounds may be poor candidates for therapeutic use.
异维A酸（13 - 顺式视黄酸）是一种人类致畸剂，在体内暴露于13 - 顺式视黄酸的小鼠胚胎表现出许多与人类相同的缺陷。在培养中暴露于13 - 顺式视黄酸的植入后早期小鼠胚胎表现出内脏弓的发育改变，类似于体内暴露后所见的改变。在几个体外系统中，某些视黄酸的苯甲酸衍生物已被证明具有等同于或大于视黄酸的活性。本研究检测了其中一些类视黄醇对体外培养的小鼠胚胎的致畸作用。将第8天的CD - 1小鼠胚胎在这些苯甲酸衍生物存在的情况下培养48小时。除Ro - 15 - 0778外，所有化合物均产生了与暴露于13 - 顺式视黄酸的胚胎中所见相似的内脏弓畸形，但有效浓度差异极大。所测试的极低浓度的视黄酸相关化合物似乎对胚胎发育有有害影响，并且这些化合物可能不是治疗用途的理想候选物。
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