The transcriptome of the uterine cervix before and after spontaneous term parturition

The transcriptome of the uterine cervix before and after spontaneous term parturition
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DOI:
10.1016/j.ajog.2006.06.021
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发表时间:
2006-09-01
影响因子:
9.8
通讯作者:
Malone, John, Jr.
Malone, John, Jr.
中科院分区:
医学1区
文献类型:
--
作者:
Hassan, Sonia S.;Romero, Roberto;Malone, John, Jr.

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目的:本研究的目的是确定差异表达的基因在人类子宫颈后自然足月labor.Study设计:宫颈组织的转录组的特点是使用AffyphineHG-U133加2微阵列。从足月未分娩(n = 7)和自然分娩(n = 9)后的患者中采集样本。微阵列统计分析包括稳健的多阵列平均值、不变探针的减少、。微分表达式的置换分析。结果:(1)未临产足月患者宫颈转录组与临产足月患者宫颈转录组差异显著;(2)未临产足月患者宫颈转录组与临产足月患者宫颈转录组差异显著;(2)独特基因(n = 1192)在自然分娩后患者宫颈组织中的表达与足月未分娩患者相比存在差异(错误发现率小于0.05,绝对倍数变化大于2);(3)基因本体分析表明,丰富了多个“生物过程”类别,包括“对生物刺激的反应”、“细胞凋亡”、“表皮发育”和“类固醇代谢”;(4)主要关注的是,参与中性粒细胞趋化性的基因在自然分娩后的妇女标本中显著上调;(5)实时定量逆转录-聚合酶链反应证实了自然分娩后患者中白细胞介素-8、白细胞介素-6和血管内皮生长因子的表达增加;(6)Toll样受体3和Toll样受体5在自然分娩后表达降低。结论:(1)基因芯片显示,足月分娩时宫颈扩张与中性粒细胞趋化性、细胞凋亡、细胞外基质调节和类固醇代谢相关基因的表达模式有关,其特征为中性粒细胞趋化性、细胞凋亡、细胞外基质调节和类固醇代谢相关基因的过度表达;(2)Toll样受体-3和Toll样受体-5在足月自然分娩过程中受到不同的调节;(3)本研究提供了一个无偏见的和全面的描述宫颈转录组的变化之前和之后自然足月分娩。(c)2006 Mosby,Inc. All rights reserved.
Objective: This study was designed to identify genes differentially expressed in the human uterine cervix after spontaneous term labor.Study design: The transcriptome of cervical tissue was characterized using Affymetrix HG-U133 plus 2 microarrays. Samples were collected from patients at term not in labor (n = 7) and after spontaneous labor (n = 9). Microarray statistical analysis included robust multiarray average, reduction of invariant probes,. and permutation analysis for differential expression. Real-time quantitative reverse transcriptase-polymerase chain reaction assays of selected genes were performed on a new set of samples from term patients without labor (n = 10) and patients after spontaneous labor (n = 9).Results: (1) The cervical transcriptome of term patients without labor was dramatically different from that of patients who underwent labor; (2) unique genes (n = 1192) were differentially expressed in the cervical tissue from patients after spontaneous labor, compared with that of the term patients without labor (false discovery rate less than 0.05, absolute fold change greater than 2); (3) Gene Ontology analysis indicated that multiple "Biological Process" categories were enriched, including "response to biotic stimulus," "apoptosis," "epidermis development," and "steroid metabolism"; (4) of major interest, genes involved in neutrophil chemotaxis were dramatically upregulated in specimens from women after spontaneous labor; (5) real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of interleukin-8, interleukin-6, and vascular endothelial growth factor in patients after spontaneous labor; and (6) Toll-like receptor-3 and Toll-like receptor-5 showed decreased gene expression in patients after spontaneous labor. This was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction.Conclusion: (1) Cervical dilatation in term labor is associated with a stereotypic gene expression pattern determined by microarray, which is characterized by overexpression of genes involved in neutrophil chemotaxis, apoptosis, extracellular matrix regulation, and steroid metabolism; (2) Toll-like receptor-3 and Toll-like receptor-5 are differentially regulated during spontaneous parturition at term; and (3) this study provides an unbiased and comprehensive description of the changes in the cervical transcriptome before and after spontaneous term labor. (c) 2006 Mosby, Inc. All rights reserved.