Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, 665, Siheung-daero, Youngdeungpo-gu, Seoul, 07442, Republic of Korea.
Institute of New Frontier Research, College of Medicine, Hallym University, Hallymdaehak-gil, Chuncheon, 24252, Republic of Korea.
Reprod Biol Endocrinol. 2021 Feb 24;19(1):32. doi: 10.1186/s12958-021-00715-2.
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.
子宫颈是妊娠期间防止上行感染的机械和免疫屏障。宫颈机能不全（CI）是一种无痛性的宫颈扩张，发生在妊娠中期，是极早产的重要原因。我们假设 CI 患者具有不同的转录组特征。因此，我们比较了 CI 患者和对照组的外周血转录组谱。
使用 RNA 测序生成 11 名 CI 患者和 4 名对照组的全基因表达谱，并进行差异表达分析，以识别 CI（n=11）和对照组（n=4）组以及 CI 早产（n=7）和 CI 足月（n=4）组之间表达差异显著的基因。根据基因本体论过程评估基因集富集情况，并通过 qRT-PCR 和 ELISA 在不同样本集中验证 CI 中差异表达的基因子集。
30 个基因在 CI 和对照组之间表达差异。CI 组上调的差异表达基因包括中性粒细胞介导的免疫相关（DEFA3 和 ELANE）和碳酸氢盐转运相关基因。CI 患者血清α防御素 3 浓度明显高于对照组（P=0.014）。根据妊娠结局分析差异基因表达，CI 足月和 CI 早产组之间有 338 个差异表达基因。CI 足月组的免疫和防御反应与机体相关基因以及流感 A 和 NOD 样受体信号通路上调。
我们的研究结果显示 CI 患者的全血转录组谱与对照组有显著差异。CI 患者的不同免疫反应可能影响妊娠结局。
