Ectopic pregnancy as a model to identify endometrial genes and signaling pathways important in decidualization and regulated by local trophoblast.

Ectopic pregnancy as a model to identify endometrial genes and signaling pathways important in decidualization and regulated by local trophoblast.
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DOI:
10.1371/journal.pone.0023595
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Horne AW
Horne AW
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Duncan WC;Shaw JL;Burgess S;McDonald SE;Critchley HO;Horne AW

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妊娠早期子宫内膜在局部滋养细胞的作用下发生蜕膜化和功能改变,目前尚不完全清楚。我们假设,输卵管异位妊娠(EP)的子宫内膜可以被询问,以确定新的基因和途径参与这些过程。从患有EP(n = 11)和宫内妊娠(IUP)(n = 13)的妇女收集妊娠匹配的子宫内膜。    从组织中提取RNA。此外,制备组织用于组织学分析以确定蜕膜化程度。我们使用Affyssin基因阵列平台,结合InhibitityPathwayAnalysis和定量RT-PCR,比较a)来自蜕膜化的EP的样品(n= 6)与非蜕膜化的样品(n = 5),和B)蜕膜化的EP(n =6)与蜕膜化匹配的IUP(n =6)样品。       以PRL和IGFBP 1的表达来确定各组的蜕膜化程度。在蜕膜化配对样本中PRL和IGFBP 1的表达没有差异,但在非蜕膜化样本中显著降低(P<0.001)。蜕膜化与428个基因的表达增加相关,包括SCARA 5(181倍),DKK 1(71倍)和PROK 1(32倍),以及230个基因的表达减少,包括MMP-7(35倍)和SFRP 4(21倍)。与这些差异表达基因相关的最重要的经典途径是自然杀伤细胞和Wnt/b-连环蛋白信号传导。局部滋养层与子宫内膜基因表达的变化少得多,增加了56个基因,包括CSH 1(8倍),减少了29个基因,包括CRISP 3(8倍)。最相关的经典途径是抗原呈递。对输卵管EP子宫内膜的研究可能会促进对蜕膜化相关基因以及邻近滋养层因素影响的新认识。这提供了以前研究没有强调的独特信息,并增加了我们对妊娠早期子宫内膜的理解。
The endometrium in early pregnancy undergoes decidualization and functional changes induced by local trophoblast, which are not fully understood. We hypothesized that endometrium from tubal ectopic pregnancy (EP) could be interrogated to identify novel genes and pathways involved in these processes. Gestation-matched endometrium was collected from women with EP (n = 11) and intrauterine pregnancies (IUP) (n = 13). RNA was extracted from the tissue. In addition, tissues were prepared for histological analysis for degree of decidualization. We compared a) the samples from EP that were decidualized (n = 6) with non-decidualized samples (n = 5), and b) the decidualized EP (n = 6) with decidualization-matched IUP (n = 6) samples using an Affymetrix gene array platform, with Ingenuity Pathway Analysis, combined with quantitative RT-PCR. Expression of PRL and IGFBP1 was used to confirm the degree of decidualization in each group. There were no differences in PRL or IGFBP1 expression in the decidualization-matched samples but a marked reduction (P<0.001) in the non-decidualized samples. Decidualization was associated with increased expression of 428 genes including SCARA5 (181-fold), DKK1 (71-fold) and PROK1 (32-fold), and decreased expression of 230 genes including MMP-7 (35-fold) and SFRP4 (21-fold). The top canonical pathways associated with these differentially expressed genes were Natural Killer Cell and Wnt/b-Catenin signaling. Local trophoblast was associated with much less alteration of endometrial gene expression with an increase in 56 genes, including CSH1 (8-fold), and a reduction in 29 genes including CRISP3 (8-fold). The top associated canonical pathway was Antigen Presentation. The study of endometrium from tubal EP may promote novel insights into genes involved in decidualization and those influenced by factors from neighboring trophoblast. This has afforded unique information not highlighted by previous studies and adds to our understanding of the endometrium in early pregnancy.
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