米非司酮对恒河猴母胎界面细胞凋亡和凋亡分子p53表达的影响

胎盘形成过程中发生活跃的细胞增殖、迁移和凋亡等活动。p53蛋白是参与调节细胞周期和凋亡过程的原癌基因。本实验用原位末端标记、蛋白印迹和免疫组织化学方法研究正常和米非司酮(RU486)处理后恒河猴母胎界面绒毛和蜕膜组织细胞凋亡及p53蛋白表达。在正常妊娠的恒河猴母胎界面,凋亡信号主要集中在合体滋养层和细胞柱内的一些滋养层细胞;p53蛋白主要定位于细胞滋养层。在母体蜕膜中,也在部分基质细胞中检测到细胞凋亡和p53蛋白表达。经过RU486处理2d后,胎盘绒毛和母体蜕膜中凋亡细胞数都显著增加,绒毛中增加的凋亡信号集中于细胞滋养层。同时,RU486处理也导致绒毛细胞滋养层和蜕膜基质细胞中p53表达明显增加。以上结果提示,在正常妊娠中,生理性的细胞凋亡和p53表达可能是控制细胞滋养层细胞增殖、保持胎盘组织动态平衡的一个重要机制;RU486终止早孕的可能途径之一是促进母胎界面细胞凋亡,推测p53参与这一过程。

Effect of RU486 on apoptosis and p53 expression at the boundary of fetal-maternal interface of rhesus monkey (Macaca mulatta)

Primate placentation involves a series of cell proliferation, immigration and apoptosis which account for the progressive tissue remodelling at the implantation site. p53 is an important proto-oncogene involved in the regulation of cell-cycle and apoptosis. To study the effect of RU486 on apoptosis and expression of p53 at the fetal-maternal interface, the location of apoptotic cells and expression of p53 were examined using in situ 3'-end labeling method, immunohistochemistry and Western blot assay at the fetal-maternal interface of normal and RU486 treated rhesus monkey. Western blot analysis showed the specificity of the anti-human antibody used with the monkey tissue. In the placenta! villi, the apoptotic nuclei were observed mainly in the syncytiotro-phoblast and part of the cytotrophoblast within the cell column; p53 protein was detected mainly in the cytotrophoblast. In the endometrium, positive signals for apoptosis and p53 were detected in some stromal cells. After two days of mifepristone treatment, the apoptotic cells increased significantly in both placenta! villi and endometrium. In the villi, the increased apoptotic nuclei were mainly localized to the cytotrophoblast. At the same time, p53-positive nuclei also increased in both villous cytotrophoblast cells and endometrial stromal cells, after the treatment of RU486. These results suggest that apoptosis and expression of p53 are essential in regulating trophoblastic homeostasis by controlling its proliferation in normal placenta, whereas the up-regulation of p53 protein may play an important role in apoptosis that happens at the fetal-maternal interface induced by RU486.