Department of Obstetrics and Gynaecology-Innenstadt, Ludwig-Maximilians-University Munich, Maistrasse 11, 80337 Munich, Germany.
J Mol Endocrinol. 2011 Aug 30;47(2):145-56. doi: 10.1530/JME-11-0002. Print 2011 Oct.
The retinoid X receptor α (RXRα) is a nuclear hormone receptor that is able to bind other nuclear receptors in a heterodimeric complex, thereby activating gene transcription. Recently, we identified enhanced expression of RXRα in extravillous trophoblasts (EVT) and villous trophoblasts (VT) of miscarried placentas. In addition, an increased number of apoptotic EVT was present in miscarried placentas. In this study, on the basis of immunocytochemical analysis, western blots, and quantitative real-time reverse transcription PCR, we could demonstrate a reduced expression of RXRα in choriocarcinoma cell lines and in human VTs after stimulation with the retinoids 9-cis-retinoic acid and all-trans-retinoic acid and the prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J(2). Furthermore, a simultaneous expression of RXRα and the apoptotic marker M30 CytoDEATH in EVT of miscarried placentas from the first trimester was shown. In EVT of control placentas from legal termination of pregnancies, no co-expression of RXRα and M30 could be detected. A likely conclusion is that RXRα plays an important role in the induction of apoptosis. Downregulation of RXRα, as observed in the tested choriocarcinoma cells and trophoblasts, might serve as a protection against apoptosis and miscarriage. In conclusion, RXRα represents a potential target in the treatment of recurrent miscarriages.
视黄醇 X 受体 α（RXRα）是一种核激素受体，能够与其他核受体形成异二聚体复合物，从而激活基因转录。最近，我们发现 RXRα在流产胎盘的绒毛外滋养细胞（EVT）和绒毛滋养细胞（VT）中的表达增强。此外，流产胎盘中存在凋亡的 EVT 数量增加。在这项研究中，基于免疫细胞化学分析、Western blot 和定量实时逆转录 PCR，我们可以证明在视黄酸 9-顺式-视黄酸和全反式视黄酸以及前列腺素 15-脱氧-Δ（12,14）-前列腺素 J（2）刺激下，绒毛膜癌细胞系和人绒毛中 RXRα 的表达减少。此外，还显示了流产胎盘 EVT 中 RXRα 和凋亡标志物 M30 CytoDEATH 的同时表达。在合法终止妊娠的对照胎盘的 EVT 中，未检测到 RXRα 和 M30 的共表达。一个可能的结论是，RXRα 在诱导细胞凋亡中起重要作用。在测试的绒毛膜癌细胞和滋养细胞中观察到的 RXRα 下调可能作为对细胞凋亡和流产的保护。总之，RXRα 是治疗复发性流产的潜在靶点。
