Determination of the transcript profile of human endometrium

Determination of the transcript profile of human endometrium
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DOI:
10.1093/molehr/gag004
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发表时间:
2003-01-01
影响因子:
4
通讯作者:
Smith, SK
Smith, SK
中科院分区:
医学2区
文献类型:
--
作者:
Borthwick, JM;Charnock-Jones, DS;Smith, SK

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人类子宫内膜对卵巢激素、雌激素和孕激素的反应,一直是几十年来研究的重点。为了了解子宫内膜生理学的这一关键方面,我们对正常子宫内膜在月经周期的增殖期和分泌期的转录丰度和转录水平的变化进行了全基因组分析。高密度寡核苷酸基因阵列包括60000个基因靶点,用于确定增生期和分泌期子宫内膜的基因表达谱。用实时荧光定量聚合酶链式反应(Real-Time-PCR)验证了阵列的结果。149个转录本的表达水平在周期的两个阶段之间存在显著差异,这两个阶段由严格的范围限制(99.99%)决定,使用局部方差值计算。这些转录本包括以前已报道的类固醇反应基因(如胎盘蛋白14和基质分解素-3)和以前未与子宫内膜生理或类固醇调节相关的新转录本(如肠道三叶因子和一些表达序列标签)。对这些基因5‘端启动子区域的检测发现了许多推测的雌激素和孕激素受体DNA结合结构域,表明这些基因对卵巢激素有直接反应。
The response of the human endometrium to the ovarian hormones, estrogen and progesterone, has been the focus of decades of research. In order to understand this critical aspect of endometrial physiology, we undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle. A high-density, oligonucleotide gene array, comprising 60000 gene targets, was used to define the gene expression profile of proliferative and secretory phase endometrium. Results from the arrays were verified using real-time PCR. The expression levels of 149 transcripts differed significantly between the two phases of the cycle determined by stringent range limits (99.99%), calculated using local variance values. These transcripts include previously documented steroidally responsive genes (such as placental protein 14 and stromelysin-3) and novel transcripts not previously linked to either endometrial physiology or steroid regulation (such as intestinal trefoil factor and a number of expressed sequence tags). Examination of the 5' promoter regions of these genes identified many putative estrogen and progesterone receptor DNA binding domains, suggesting a direct response of these genes to the ovarian hormones.