本文選題：子宮基質(zhì)細胞　切入點：蛻膜化　出處：《福建醫(yī)科大學》2015年博士論文

【摘要】：小鼠子宮基質(zhì)細胞蛻膜化是小鼠胚胎植入后發(fā)生的重要事件,是以子宮基質(zhì)細胞的大量增殖、分化和細胞多核化為特征的過程。蛻膜功能的正常發(fā)揮,對胚胎著床、妊娠建立與維持,以及分娩起動均起著極為重要的作用,因此研究蛻膜的生長和調(diào)控,對于明確胚胎著床機制和生育調(diào)節(jié)都有著極為重要的意義。隨著對基質(zhì)細胞蛻膜化發(fā)生及其調(diào)控機制研究的不斷深入,科研人員對早期妊娠過程中蛻膜細胞增殖與分化及調(diào)節(jié)因素也越來越重視,并且取得了相應進展。同源框轉(zhuǎn)錄因子Prx2在胚胎發(fā)育的整個進程均有表達,尤其在間充質(zhì)細胞的分化中發(fā)揮重要的調(diào)節(jié)作用。Prx2作為轉(zhuǎn)錄因子在物種多樣性的選擇過程中,其序列始終表現(xiàn)出高度的保守性。為研究和探討Prx2在小鼠子宮基質(zhì)細胞蛻膜化中的表達以及如何調(diào)節(jié)子宮基質(zhì)細胞蛻膜化的過程,我們首先利用原位雜交的方法檢測Prx2在小鼠圍植入期子宮和人工誘導蛻膜化子宮中的表達,實驗結(jié)果顯示Prx2 mRNA在小鼠圍植入期子宮中圍繞發(fā)生蛻膜化的基質(zhì)細胞表達,在人工誘導蛻膜化子宮中亦有類似表達模式,同時Prx2在體外培養(yǎng)基質(zhì)細胞中也有表達。為進一步闡明Prx2在體內(nèi)、外基質(zhì)細胞蛻膜化過程中的調(diào)節(jié)作用,我們構(gòu)建了過表達Prx2的腺病毒,并在體內(nèi)、外對基質(zhì)細胞進行感染。結(jié)果顯示Prx2在體內(nèi)、外基質(zhì)細胞中表達均被明顯提升,同時蛻膜化標志性分子Dtprp的表達因Prx2的高表達而被明顯下調(diào)。進一步的實驗結(jié)果顯示,轉(zhuǎn)錄因子Prx2過表達的細胞中,甘油三酯水解限速酶Atgl和脂肪酸β-氧化限速酶Cpt1a的表達下調(diào),致使過表達Prx2細胞中的脂肪滴堆積,最終導致了蛻膜化的異常過程。本課題首次探討了Prx2在小鼠體內(nèi)外子宮基質(zhì)細胞中的表達模式以及通過影響Atgl的表達調(diào)控蛻膜細胞中脂肪酸代謝,進而調(diào)節(jié)小鼠子宮基質(zhì)細胞向蛻膜化細胞轉(zhuǎn)變過程。
[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.
【學位授予單位】：福建醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R321

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