| 研究生: |
黃靜如 Huang, Ching-Ju |
|---|---|
| 論文名稱: |
DAZL及其相關之細胞週期調控者在黃體的表現 Expression DAZL and its associated cell cycle regulators in corpus luteum |
| 指導教授: |
郭保麟
Kuo, Paolink 蔡少正 Tsai, Shaw-Jenq |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 分子醫學研究所 Institute of Molecular Medicine |
| 論文出版年: | 2003 |
| 畢業學年度: | 91 |
| 語文別: | 中文 |
| 論文頁數: | 109 |
| 中文關鍵詞: | 黃體 、細胞週期 、顆粒細胞 |
| 外文關鍵詞: | corpus, granulosa cell, DAZL, DAZAP1, MPF, CDC25C, CDC25B, CDC25A |
| 相關次數: | 點閱:113 下載:3 |
| 分享至: |
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在人類的Y染色體有個與造精功能相關的基因稱之DAZ (deleted in Azoospermia) 基因,此基因若發生缺失,會對造精功能造成影響。DAZ基因在人類2 號及3 號染色體的同源基因,分別為BOULE 及DAZL(DAZL-Like)基因,目前研究認為DAZL 基因可能是生殖細胞中的細胞週期調控者,例如在老鼠中,dazl 對於完成減數分裂的過程中,扮演一個不可或缺的角色,在果蠅中將dazl (boule)基因阻斷後 會讓生殖細胞停留在減數分裂之G2 至M 週期中,DAZ 基因成員(DAZ 、DAZL和BOULE)可能是CDC25 下游的調控蛋白,其作用為活化MPF,MPF是一複合體包括cdk1、cdk2、cyclin A1、cyclinA2、cyclin B1 及cyclin B2。在我的研究中首先先選殖老鼠的dazl 基因全長,並在人類及老鼠的黃體中偵測到DAZL 蛋白的表現,同時在人類黃體化之濾泡細胞發現DAZL 及其相關之DAZAP1 蛋白也有表現,我們進一步利用老鼠為實驗模式以HCG 誘發DAZL 蛋白的產生,並從臨床角度觀察到DAZL的表現量可能與誘導排卵的反應好壞有關。排卵後的濾泡組織會分化形成黃體,黃體會合成大量的黃體激素(progesterone;P4)及DAZL,由於DAZL在非生殖細胞(luteal cell)也有表現,推測與DAZL 相關的蛋白也可能在luteal cell 有表現,果真發現cdc25a,、cdc25b、cdc25c、cyclin A、cyclin B1、cyclin B2 cdk1 和cdk2 表現在黃體化後的濾泡組織,其表現型態都很似。我們推測DAZL 及其相關之細胞週期調控蛋白可能是調控黃體的細胞週期使黃體細胞不再進行有絲分裂
The human DAZ (Deleted in Azoospermia) gene family contains a cluster of DAZ gene on the Y chromosome, a single copy of autosomal homologue,DAZL(DAZ-Like) mapped to chromosome 3p24 and BOULE mapped to chromosome 2. DAZL was previously identified as a germ-line specific cell cycle regulator. In mice, dazl is necessary for completion of meiosis. In Drosophila the dazl (boule) knockout mutant has a block in G2/M of meiosis, a phenotype very much similar to mutant of CDC25 homologue (Twine). It has been proposed that DAZ gene family may be the
upstream regulator of CDC25, which regulates activation of maturation promoting factor (MPF) – a complex consisting of cdk1, cdk2, cyclin A1,
A2 (or B1, B2) in mammalian cells. In this study, I cloned the full-length dazl cDNA of rat. It was found that DAZL protein is expressed rat and human corpus luteum. I also found expression of DAZL and its associated protein DAZAP1 in human luteinized granulose cells. Using a rat model, I showed induction of DAZL protein by hCG. In women who underwent IVF treatment for infertility, DAZL protein may be an indicator of response to ovulation induction. The corpus luteum (CL) is a transient endocrine organ, whose primary secretary product, progesterone, is required for maintenance
of pregnancy. The finding of DAZL protein expression in non-germ cells (luteal cells) prompts me to test the expression of DAZL-associated cell
cycle regulators in luteal cells. I found similar expression pattern of cdc25a,cdc25b, cdc25c, cyclin A, cyclin B1, cyclin B2, cdk1, and cdk2 in rat and
human ovary. All of these cell-cycle regulators seem to be induced afterluteinization of granulosa cells. It is hypothesized that DAZL protein and
its associated cell-cycle regulators may play important roles in the regulation of CL function of mammalian species. Knock-down experiments based on RNAi is now ongoing to explore the roles DAZL in regulation of cellular differentiation.
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