J Perinat Med. 2013 Nov;41(6):665-81. doi: 10.1515/jpm-2013-0086.
The molecular basis of failure to progress in labor is poorly understood. This study was undertaken to characterize the myometrial transcriptome of patients with an arrest of dilatation (AODIL).
Human myometrium was prospectively collected from women in the following groups: (1) spontaneous term labor (TL; n=29) and (2) arrest of dilatation (AODIL; n=14). Gene expression was characterized using Illumina® HumanHT-12 microarrays. A moderated Student's t-test and false discovery rate adjustment were used for analysis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of selected genes was performed in an independent sample set. Pathway analysis was performed on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). The MetaCore knowledge base was also searched for pathway analysis.
(1) Forty-two differentially expressed genes were identified in women with an AODIL; (2) gene ontology analysis indicated enrichment of biological processes, which included regulation of angiogenesis, response to hypoxia, inflammatory response, and chemokine-mediated signaling pathway. Enriched molecular functions included transcription repressor activity, heat shock protein (Hsp) 90 binding, and nitric oxide synthase (NOS) activity; (3) MetaCore analysis identified immune response chemokine (C-C motif) ligand 2 (CCL2) signaling, muscle contraction regulation of endothelial nitric oxide synthase (eNOS) activity in endothelial cells, and triiodothyronine and thyroxine signaling as significantly overrepresented (false discovery rate <0.05); (4) qRT-PCR confirmed the overexpression of Nitric oxide synthase 3 (NOS3); hypoxic ischemic factor 1A (HIF1A); Chemokine (C-C motif) ligand 2 (CCL2); angiopoietin-like 4 (ANGPTL4); ADAM metallopeptidase with thrombospondin type 1, motif 9 (ADAMTS9); G protein-coupled receptor 4 (GPR4); metallothionein 1A (MT1A); MT2A; and selectin E (SELE) in an AODIL.
The myometrium of women with AODIL has a stereotypic transcriptome profile. This disorder has been associated with a pattern of gene expression involved in muscle contraction, an inflammatory response, and hypoxia. This is the first comprehensive and unbiased examination of the molecular basis of an AODIL.
分娩进展失败的分子基础尚未完全阐明。本研究旨在对扩张停滞（AODIL）患者的子宫肌层转录组进行特征描述。
前瞻性采集以下人群的人子宫肌层组织：（1）自发性足月分娩（TL；n=29）和（2）扩张停滞（AODIL；n=14）。使用 Illumina® HumanHT-12 微阵列进行基因表达特征描述。采用调节学生 t 检验和错误发现率调整进行分析。使用独立样本集进行选定基因的定量逆转录-聚合酶链反应（qRT-PCR）。使用京都基因与基因组百科全书（KEGG）途径数据库中的途径分析与重叠基因弱化（PADOG）对途径分析进行加权。还在 MetaCore 知识库中搜索了途径分析。
（1）在患有 AODIL 的女性中鉴定出 42 个差异表达基因；（2）基因本体论分析表明，生物学过程富集，包括血管生成的调节、缺氧反应、炎症反应和趋化因子介导的信号通路。丰富的分子功能包括转录抑制因子活性、热休克蛋白（Hsp）90 结合和一氧化氮合酶（NOS）活性；（3）MetaCore 分析确定了免疫反应趋化因子（C-C 基序）配体 2（CCL2）信号、内皮细胞中内皮型一氧化氮合酶（eNOS）活性的肌肉收缩调节、三碘甲状腺原氨酸和甲状腺素信号作为显著过度表达（错误发现率<0.05）；（4）qRT-PCR 证实了一氧化氮合酶 3（NOS3）；缺氧诱导因子 1A（HIF1A）；趋化因子（C-C 基序）配体 2（CCL2）；血管生成素样 4（ANGPTL4）；含金属蛋白酶结构域的金属蛋白酶 13（ADAM13）；载脂蛋白 E（APOE）；G 蛋白偶联受体 4（GPR4）；金属硫蛋白 1A（MT1A）；金属硫蛋白 2A（MT2A）；选择素 E（SELE）在 AODIL 中过表达。
AODIL 妇女的子宫肌层具有典型的转录组谱。这种疾病与肌肉收缩、炎症反应和缺氧相关的基因表达模式有关。这是对 AODIL 分子基础的首次全面和无偏检验。
