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着床窗口期的基因谱分析:来自人类和啮齿动物模型的微阵列分析

Gene profiling the window of implantation: Microarray analyses from human and rodent models.

作者信息

Herington Jennifer L, Guo Yan, Reese Jeff, Paria Bibhash C

机构信息

Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Department of Cancer Biology and Vanderbilt Technologies for Advanced Genomics Analysis and Research Design, Vanderbilt University, Nashville, TN 37232, USA.

出版信息

J Reprod Health Med. 2016 Dec;2(Suppl 2):S19-S25. doi: 10.1016/j.jrhm.2016.11.006. Epub 2016 Dec 9.

Abstract

Poor uterine receptivity leads to implantation defects or failure. Identification of uterine molecules crucial to uterine receptivity and/or embryo implantation provides the opportunity to design a diagnostic screening toolkit for uterine receptivity or targeted drug discovery for treating implantation-based infertility. In this regard, gene-profiling studies performed in humans and rodents have identified numerous genes involved in the transcriptional regulation of uterine receptivity and embryo implantation. In this article, we compared available uterine microarray datasets collected during the time of uterine receptivity and implantation in humans, mice and hamsters to uncover conserved gene sets. We also compared the transcriptome signature of women with unexplained infertility (UIF) and recurrent implantation failure (RIF) to gain insight into genes potentially dysregulated during endometrial receptivity or embryo implantation. Among numerous differentially expressed genes, few were revealed that might have molecular diagnostic screening potential for identifying the uterine receptive state during the time of implantation. Finally, functional annotation of gene sets uncovered altered uterine apoptosis or cell adhesion pathways in women with UIF and RIF, respectively. These conserved or divergent gene sets provide insights into the uterine receptive state for supporting blastocyst implantation.

摘要

子宫容受性差会导致着床缺陷或失败。鉴定对子宫容受性和/或胚胎着床至关重要的子宫分子,为设计子宫容受性诊断筛查工具或治疗基于着床的不孕症的靶向药物发现提供了机会。在这方面,在人类和啮齿动物中进行的基因谱研究已经鉴定出许多参与子宫容受性和胚胎着床转录调控的基因。在本文中,我们比较了在人类、小鼠和仓鼠子宫容受性和着床期间收集的可用子宫微阵列数据集,以发现保守的基因集。我们还比较了不明原因不孕症(UIF)和反复着床失败(RIF)女性的转录组特征,以深入了解在子宫内膜容受性或胚胎着床期间可能失调的基因。在众多差异表达基因中,很少有基因被揭示可能具有在着床期间识别子宫容受状态的分子诊断筛查潜力。最后,基因集的功能注释分别揭示了UIF和RIF女性子宫凋亡或细胞粘附途径的改变。这些保守或不同的基因集为支持囊胚着床的子宫容受状态提供了见解。

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