Pathogenesis of retinoic acid-induced spina bifida in rat embryos

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In a previous study, we showed that the intrauterine exposure of rat embryos to retinoic acid (RA) in the organogenesis period (8-11 days of gestation) induced various malformations according to the dose and timing of RA administration. Analysis of the characteristics of RA-induced malformation showed that many of them arose from the lumbosacrocaudal region of the axial skeleton. Based on these results, the present study was focused on the elucidation of the pathogenesis of spina bifida. All-trans RA was administered at dose of 60 mg/kg to pregnant DA rats at 10 days of gestation, and its influence on the posterior neuropore of embryos was examined serially by morphological methods. As a result, neural plate elevation was impaired at 6-9 h after RA administration, and neuroepithelial eversion occurred 12 h after administration. Thereafter, neuroepithelial eversion due to neuroepithelial overgrowth occurred, presumbly leading to the development of spina bifida.
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