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A comparison of transcriptomic profiles in endometrium during window of implantation between women with unexplained recurrent implantation failure and recurrent miscarriage

机译:原因不明的反复着床失败和反复流产的女性在着床期间子宫内膜转录组特征的比较

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The endometrium becomes receptive to the embryo only in the mid-luteal phase, but not in the other stages of the menstrual cycle. Endometrial factors play an important role in implantation. Women with recurrent miscarriage and recurrent implantation failure have both been reported to have altered expression of receptivity markers during the window of implantation. We aimed to compare the gene expression profiles of the endometrium in the window of implantation among women with unexplained recurrent implantation failures (RIF) and unexplained recurrent miscarriages (RM) by RNA sequencing (RNA-Seq). In total 20 patients (9 RIF and 11 RM) were recruited. In addition 4 fertile subjects were included as reference. Endometrium samples were precisely timed on the 7th day after luteal hormone surge (LH?+?7). All the 24 endometrium samples were extracted for total RNA. The transcriptome was determined by RNA-Seq in the first 14 RNA samples (5 RIF, 6 RM and 3 fertile). Differentially expressed genes between RM and RIF were validated by quantitative real-time PCR (qPCR) in all 24 RNA samples (9 RIF, 11 RM and 4 fertile). Transcriptomic profiles of RM and RIF, but not control samples, were separated from each other by principle component analysis (PCA) and support vector machine (SVM). Complementary and coagulation cascades pathway was significantly up-regulated in RIF while down-regulated in RM. Differentially expressed genes C3, C4, C4BP, DAF, DF and SERPING1 in complement and coagulation cascade pathway between RM and RIF were further validated by qPCR. This study compared endometrial transcriptome among patients with RIF and RM in the window of implantation; it identified differential molecular pathways in endometrium between RIF and RM, which potentially affect the implantation process.
机译:子宫内膜仅在黄体中期才接受胚胎,而在月经周期的其他阶段则不接受。子宫内膜因素在植入中起重要作用。据报道,反复流产和反复着床失败的女性在着床期间都改变了接受性标志物的表达。我们旨在通过RNA测序(RNA-Seq)比较原因不明的反复植入失败(RIF)和原因不明的反复流产(RM)的女性在植入窗口内子宫内膜的基因表达谱。总共招募了20位患者(9位RIF和11位RM)。另外,包括4个可育受试者作为参考。在黄体激素激增后第7天精确测定子宫内膜的时间(LHβ+β7)。提取所有24个子宫内膜样品的总RNA。通过RNA-Seq在前14个RNA样品(5个RIF,6个RM和3个可育)中确定转录组。通过定量实时PCR(qPCR)在所有24个RNA样品(9个RIF,11个RM和4个可育)中验证了RM和RIF之间差异表达的基因。通过主成分分析(PCA)和支持向量机(SVM)相互分离了RM和RIF的转录组谱,但没有分离对照样品。互补和凝血级联途径在RIF中显着上调,而在RM中则下调。通过qPCR进一步验证了RM和RIF之间补体和凝血级联途径中差异表达的基因C3,C4,C4BP,DAF,DF和SERPING1。这项研究比较了在植入窗口中RIF和RM患者的子宫内膜转录组。它鉴定出子宫内膜在RIF和RM之间的差异分子途径,这可能影响植入过程。

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