同源盒转录因子Prx2对小鼠子宫基质细胞蜕膜分化的调控研究

发布时间：2018-03-26 11:22

本文选题：子宫基质细胞　切入点：蜕膜化　出处：《福建医科大学》2015年博士论文

【摘要】：小鼠子宫基质细胞蜕膜化是小鼠胚胎植入后发生的重要事件,是以子宫基质细胞的大量增殖、分化和细胞多核化为特征的过程。蜕膜功能的正常发挥,对胚胎着床、妊娠建立与维持,以及分娩起动均起着极为重要的作用,因此研究蜕膜的生长和调控,对于明确胚胎着床机制和生育调节都有着极为重要的意义。随着对基质细胞蜕膜化发生及其调控机制研究的不断深入,科研人员对早期妊娠过程中蜕膜细胞增殖与分化及调节因素也越来越重视,并且取得了相应进展。同源框转录因子Prx2在胚胎发育的整个进程均有表达,尤其在间充质细胞的分化中发挥重要的调节作用。Prx2作为转录因子在物种多样性的选择过程中,其序列始终表现出高度的保守性。为研究和探讨Prx2在小鼠子宫基质细胞蜕膜化中的表达以及如何调节子宫基质细胞蜕膜化的过程,我们首先利用原位杂交的方法检测Prx2在小鼠围植入期子宫和人工诱导蜕膜化子宫中的表达,实验结果显示Prx2 mRNA在小鼠围植入期子宫中围绕发生蜕膜化的基质细胞表达,在人工诱导蜕膜化子宫中亦有类似表达模式,同时Prx2在体外培养基质细胞中也有表达。为进一步阐明Prx2在体内、外基质细胞蜕膜化过程中的调节作用,我们构建了过表达Prx2的腺病毒,并在体内、外对基质细胞进行感染。结果显示Prx2在体内、外基质细胞中表达均被明显提升,同时蜕膜化标志性分子Dtprp的表达因Prx2的高表达而被明显下调。进一步的实验结果显示,转录因子Prx2过表达的细胞中,甘油三酯水解限速酶Atgl和脂肪酸β-氧化限速酶Cpt1a的表达下调,致使过表达Prx2细胞中的脂肪滴堆积,最终导致了蜕膜化的异常过程。本课题首次探讨了Prx2在小鼠体内外子宫基质细胞中的表达模式以及通过影响Atgl的表达调控蜕膜细胞中脂肪酸代谢,进而调节小鼠子宫基质细胞向蜕膜化细胞转变过程。
[Abstract]:Decidualization of mouse uterine stromal cells is an important event after implantation of mouse embryo. The establishment and maintenance of pregnancy, as well as the initiation of labor, play an extremely important role in the study of the growth and regulation of decidua. It is of great significance to clarify the mechanism of embryo implantation and regulation of fertility. With the development of the study of decidualization and regulation of stromal cells, Researchers pay more and more attention to the factors of proliferation, differentiation and regulation of decidual cells during early pregnancy, and have made corresponding progress. Homobox transcription factor Prx2 is expressed in the whole process of embryonic development. In particular, Prx2 plays an important regulatory role in the differentiation of mesenchymal cells. Prx2, as a transcription factor, plays an important role in the selection of species diversity. In order to study the expression of Prx2 in decidualization of mouse stromal cells and how to regulate the process of decidualization of uterine stromal cells. We first detected the expression of Prx2 in mouse periimplantation uterus and artificially induced decidualized uterus by in situ hybridization. The results showed that Prx2 mRNA was expressed around decidualized stromal cells in mouse periimplantation uterus. A similar expression pattern was found in artificially induced decidualized uterus, and Prx2 was also expressed in stromal cells in vitro. In order to elucidate the regulatory role of Prx2 during decidualization in vivo and in vitro, We constructed an adenovirus that overexpressed Prx2 and infected stromal cells in vivo and in vitro. The results showed that the expression of Prx2 was significantly increased in vivo and in extracellular stromal cells. At the same time, the expression of decidualized iconic molecule Dtprp was significantly down-regulated by the high expression of Prx2. Further experimental results showed that the transcription factor Prx2 overexpressed in cells, The expression of triglyceride hydrolytic rate-limiting enzyme (Atgl) and fatty acid 尾 -oxidation rate-limiting enzyme (Cpt1a) was down-regulated, resulting in the accumulation of fat droplets in the over-expressed Prx2 cells. In this study, the expression pattern of Prx2 in mouse uterine stromal cells in vitro and in vivo and the regulation of fatty acid metabolism in decidua cells by affecting the expression of Atgl were investigated for the first time. Furthermore, the transformation of mouse uterine stromal cells to decidualized cells was regulated.
【学位授予单位】：福建医科大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R321

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