Roulier S, Rochette-Egly C, Rebut-Bonneton C, Porquet D, Evain-Brion D
Laboratoire de Physiopathologie du Développement, CNRS URA 1337, ENS, Paris, France.
Mol Cell Endocrinol. 1994 Nov;105(2):165-73. doi: 10.1016/0303-7207(94)90166-x.
Vitamin A is an important factor during gestation and its metabolite, retinoic acid (RA), is a potent teratogen. However, RA action on the placenta is still poorly understood. In this study we analysed the presence of RARs and RXRs in human trophoblastic cells. We determined that RAR alpha was the more expressed form in term placenta, and that RAR beta was induced by RA treatment. Then we analysed RA effects on endocrine activities and on epidermal growth factor (EGF) receptor expression. We found that RA decreased 125I-labeled EGF binding and EGF-dependent phosphorylation. Furthermore, RA treatment led to a concentration-dependent decrease in the amount of EGFR protein expression. This treatment also decreased EGF receptor mRNA levels, suggesting transcriptional regulation of the EGF receptor. Thus we demonstrated that RA could interact with feto-placental development by modulating trophoblast EGF receptors expression, probably via its nuclear receptors.
维生素A是孕期的一个重要因素,其代谢产物视黄酸(RA)是一种强效致畸剂。然而,RA对胎盘的作用仍知之甚少。在本研究中,我们分析了人类滋养层细胞中视黄酸受体(RARs)和视黄醇X受体(RXRs)的存在情况。我们确定RARα是足月胎盘中表达较多的形式,且RARβ可被RA处理诱导表达。然后我们分析了RA对内分泌活性和表皮生长因子(EGF)受体表达的影响。我们发现RA降低了125I标记的EGF结合及EGF依赖性磷酸化。此外,RA处理导致EGFR蛋白表达量呈浓度依赖性下降。该处理还降低了EGF受体mRNA水平,提示存在对EGF受体的转录调控。因此我们证明,RA可能通过其核受体调节滋养层EGF受体表达,从而与胎儿-胎盘发育相互作用。