Jiang H, Gyda M, Harnish D C, Chandraratna R A, Soprano K J, Kochhar D M, Soprano D R
Department of Anatomy and Developmental Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Teratology. 1994 Jul;50(1):38-43. doi: 10.1002/tera.1420500106.
Retinoic acid (RA) plays an important role during normal embryogenesis, however high doses of RA are teratogenic. Retinoic acid receptor-beta 2 (RAR-beta 2) mRNA and protein levels were previously demonstrated to undergo rapid elevation in susceptible tissues after treatment with teratogenic doses of RA. In this report we compared the effects of a number of retinoids, which represent a wide variety of chemical structures and which differ in their teratogenic potencies, on RAR-beta 2 mRNA levels in mouse embryos 6 hr after treatment. Retinoid treatments which result in a high incidence of limb defects elevated RAR-beta 2 mRNA levels similarly (10-14 fold in the limb buds, 4-8 fold in the head, and 2-4 fold in the remainder of the body). On the other hand, retinoid treatments which cause a low or no incidence of limb defects resulted in minor changes in RAR-beta 2 mRNA levels in each embryonic region. Therefore, a strong positive correlation was found between the elevation of RAR-beta 2 mRNA levels and the retinoids which produce limb defects. This provides further evidence that an elevation of RAR-beta 2 mRNA levels, and subsequently protein levels, is an important event involved in mediating the effects of RA during dysmorphogenesis.
视黄酸（RA）在正常胚胎发育过程中发挥着重要作用，然而高剂量的RA具有致畸性。先前已证明，用致畸剂量的RA处理后，视黄酸受体β2（RAR-β2）的mRNA和蛋白质水平在易感组织中会迅速升高。在本报告中，我们比较了多种类视黄醇（它们代表了广泛的化学结构，致畸效力也不同）对处理6小时后的小鼠胚胎中RAR-β2 mRNA水平的影响。导致肢体缺陷发生率高的类视黄醇处理同样提高了RAR-β2 mRNA水平（在肢芽中提高了10 - 14倍，在头部提高了4 - 8倍，在身体其他部位提高了2 - 4倍）。另一方面，导致肢体缺陷发生率低或无肢体缺陷的类视黄醇处理在每个胚胎区域导致RAR-β2 mRNA水平的变化较小。因此，在RAR-β2 mRNA水平升高与产生肢体缺陷的类视黄醇之间发现了很强的正相关性。这进一步证明，RAR-β2 mRNA水平以及随后的蛋白质水平升高是在畸形发生过程中介导RA作用的一个重要事件。
