Frenz D A, Liu W
Department of Otolaryngology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Teratology. 1997 Oct;56(4):233-40. doi: 10.1002/(SICI)1096-9926(199710)56:4<233::AID-TERA1>3.0.CO;2-#.
Previous studies have shown that in utero exposure of the mouse embryo to nonphysiological levels of all-trans retinoic acid (RA) produces malformations of the epithelial-derived auditory and vestibular receptors of the inner ear and its surrounding cartilaginous capsule. In this study, we demonstrate the effects of all-trans RA in high-density cultures of the periotic mesenchyme fated to form the otic capsule. Our results demonstrate an inhibition of chondrogenesis in cultured periotic mesenchyme + otic epithelium of embryonic age E10.5 days (E10.5) in response to all-trans RA exposure. However, at later stages of development (i.e., E12, E14), when epithelial-mesenchymal interactions are no longer required for initiation of chondrogenesis, exposure to this teratogen has no effect on the chondrogenic process. Two analogues of all-trans RA, i.e., cis-RA and trans-retinol, were investigated for their biological activity in chondrogenic cultures of inner ear mesenchyme + epithelium. Moreover, we tested the inductive capability and responsiveness of in utero RA-exposed inner ear tissues when cultured with inner ear tissues that were not exposed to this teratogen. Our results support the hypothesis that all-trans RA disrupts otic capsule formation by interfering with the tissue interactions required for its normal differentiation and development.
先前的研究表明，在子宫内将小鼠胚胎暴露于非生理水平的全反式视黄酸（RA）会导致内耳及其周围软骨囊的上皮衍生听觉和前庭感受器出现畸形。在本研究中，我们展示了全反式RA对注定要形成耳囊的耳周间充质高密度培养物的影响。我们的结果表明，在胚胎龄E10.5天（E10.5）的培养耳周间充质+耳上皮中，响应全反式RA暴露会抑制软骨生成。然而，在发育的后期阶段（即E12、E14），当软骨生成的起始不再需要上皮-间充质相互作用时，暴露于这种致畸剂对软骨生成过程没有影响。研究了全反式RA的两种类似物，即顺式RA和反式视黄醇，它们在内耳间充质+上皮的软骨生成培养物中的生物活性。此外，我们测试了子宫内暴露于RA的内耳组织与未暴露于这种致畸剂的内耳组织一起培养时的诱导能力和反应性。我们的结果支持这样的假设，即全反式RA通过干扰耳囊正常分化和发育所需的组织相互作用来破坏耳囊形成。
