Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.

Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.
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DOI:
10.1186/s12958-021-00715-2
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发表时间:
2021-02-24
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Park ST
Park ST
中科院分区:
其他
文献类型:
--
作者:
Son GH;Choi SY;Ju YJ;Lee KY;Lee JJ;Song JE;Kim Y;Park ST

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子宫宫颈是一个机械和免疫屏障,防止上升感染在怀孕期间。宫颈功能不全(CI)是发生在妊娠中期的无痛宫颈扩张,是极早产的重要原因。我们假设患有CI的女性具有不同的转录组特征。因此,我们比较了CI女性和对照组的外周血转录组学特征。采用RNA测序方法生成11例CI妇女和4例对照组的整体基因表达谱,并进行差异表达分析,以鉴定CI组(n = 11)和对照组(n = 4)以及CI-早产儿组(n = 7)和CI-term组(n = 4)之间表达变化显著的基因。根据基因本体过程评估基因集的富集程度,并通过qRT-PCR和ELISA在不同的样本集中验证CI中差异表达的基因子集。30个基因在CI组和对照组之间有差异表达。CI组中差异上调的基因包括中性粒细胞介导的免疫相关基因(DEFA3和ELANE)和碳酸氢盐运输相关基因。CI患者血清α -防御素3浓度显著高于对照组(P = 0.014)。根据妊娠结局对差异基因表达进行分析,发现在ci足月组和ci早产儿组之间存在338个差异表达基因。在CI-term组中,机体相关基因、甲型流感和nod样受体信号通路的免疫和防御反应上调。我们的研究结果显示,与对照组相比,CI女性的全血转录组谱存在显著差异。CI妇女不同的免疫反应可能影响妊娠结局。在线版本包含补充材料,可在10.1186/s12958-021-00715-2获得。
The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes. The online version contains supplementary material available at 10.1186/s12958-021-00715-2.
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