ENDOGENOUS DISTRIBUTION OF RETINOIDS DURING NORMAL DEVELOPMENT AND TERATOGENESIS IN THE MOUSE EMBRYO
ENDOGENOUS DISTRIBUTION OF RETINOIDS DURING NORMAL DEVELOPMENT AND TERATOGENESIS IN THE MOUSE EMBRYO
复制标题
DOI：
10.1002/aja.1002020310
复制
发表时间：
1995-03-01
影响因子：
2.5
通讯作者：
MADEN, M
中科院分区：
文献类型：
--
作者：
HORTON, C;MADEN, M
我们已经分析了内源性类维生素A存在于整个小鼠胚胎从第9天到第14天的发展和在两个阶段，第10.5天和第13天，通过HPLC胚胎的个别组件。我们只能检测到两种类维生素A，全反式-RA（tRA）和全反式-视黄醇（t-retinol），而t-retinol是tRA的5 - 10倍。我们不能检测到9-顺式RA或任何didehydroretinoids，因此哺乳动物胚胎似乎不同，从其他胚胎，如鸡，非洲爪蟾，和鱼的类维生素A含量。在6天的发展分析中，tRA的水平没有显着变化，而t-视黄醇急剧上升，肝脏的发展。在胚胎内，tRA在发育中的脊髓中以高水平存在，而在前脑中以非常低的水平存在;事实上，从前脑到脊髓存在内源性tRA的梯度。胚胎的其他部分有中等水平的tRA。当对10.5天的胚胎给予致畸剂量的RA时，胚胎个体组织中存在的tRA水平急剧上升-从175倍上升到1,400倍-并且在所有组织中水平都上升，而不是在任何专有区域。然后，我们确定了胚胎的哪些区域因这种致畸剂量而畸形。下颌、腭、椎骨、尾巴和四肢始终异常，由于这些区域接受的tRA剂量不高于任何其他区域，因此得出结论，细胞特异性因素必须决定这些组织的致畸反应。然后，我们考虑是否细胞视黄酸结合蛋白I或II（CRABP I或II）在这种反应中发挥任何作用，通过确定其在每个组织中的相对水平进行分析。CRABP I和II的存在与RA的分布之间没有相关性。CRABP I和II的存在与致畸位点之间也没有明确的相关性。因此，我们得出结论，其他因素，如核因素，必须负责的致畸反应，RA。(C)1995 Wiley-Liss，Inc.
We have analysed the endogenous retinoids present in whole mouse embryos from day 9 to day 14 of development and in individual components of the embryo at two stages, day 10.5 and day 13, by HPLC. We can only detect two retinoids, all-trans-RA (tRA) and all-trans-retinol (t-retinol), and t-retinol is 5-10-fold in excess over tRA. We cannot detect 9-cis-RA or any didehydroretinoids; thus mammalian embryos seem to differ in their retinoid content from other embryos such as chick, Xenopus, and fish. The levels of tRA do not change significantly over the 6 days of development analysed, whereas t-retinol rises sharply as the liver develops. Within the embryo, tRA is present at high levels in the developing spinal cord and at very low levels in the forebrain; indeed there is a gradient of endogenous tRA from the forebrain to the spinal cord. Other parts of the embryo had intermediate levels of tRA. When a teratogenic dose of RA was administered to day 10.5 embryos, the levels of tRA present in individual tissues of the embryo rose dramatically-from 175-fold to 1,400-fold-and the levels rose in all tissues not in any exclusive areas. We then determined which areas of the embryo were malformed by such a teratogenic dose. The lower jaw, palate, vertebrae, tail, and limbs were consistently abnormal, and since these areas received a dose of tRA no higher than any other it was concluded that cell-specific factors must determine the teratogenic response of these tissues. We then considered whether cellular retinoic acid-binding protein I or II (CRABP I or II) played any role in this response by determining their relative levels in each of the tissues analysed. There was no correlation between the presence of CRABP I and II and the distribution of administered RA. Neither was there a clear correlation in detail between the presence of CRABP I and II and the sites of teratogenesis. We therefore conclude that other factors, for example, nuclear factors, must be responsible for the teratogenic response to RA. (C) 1995 Wiley-Liss, Inc.