Huang Jin, Qin Hao, Yang Yihua, Chen Xiaoyan, Zhang Jiamiao, Laird Susan, Wang Chi Chiu, Chan Ting Fung, Li Tin Chiu
Department of Obstetrics and Gynaecology.
School of Life SciencesThe Chinese University of Hong KongHong Kong SAR, China.
Reproduction. 2017 Jun;153(6):749-758. doi: 10.1530/REP-16-0574. Epub 2017 Mar 10.
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 and 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.
子宫内膜仅在黄体中期才对胚胎具有容受性,而在月经周期的其他阶段则不具有。子宫内膜因素在着床过程中起着重要作用。据报道,反复流产和反复着床失败的女性在着床窗口期容受性标志物的表达均发生了改变。我们旨在通过RNA测序(RNA-Seq)比较不明原因反复着床失败(RIF)和不明原因反复流产(RM)女性在着床窗口期子宫内膜的基因表达谱。总共招募了20名患者(9名RIF和11名RM)。此外,纳入4名有生育能力的受试者作为对照。在黄体生成素激增后第7天(LH + 7)精确采集子宫内膜样本。提取所有24份子宫内膜样本的总RNA。对前14份RNA样本(5名RIF、6名RM和3名有生育能力者)进行RNA-Seq以确定转录组。通过定量实时PCR(qPCR)在所有24份RNA样本(9名RIF、11名RM和4名有生育能力者)中验证RM和RIF之间的差异表达基因。通过主成分分析(PCA)和支持向量机(SVM),RM和RIF的转录组图谱彼此分离,但对照样本未分离。RIF中补体和凝血级联途径显著上调,而RM中则下调。通过qPCR进一步验证RM和RIF在补体和凝血级联途径中的差异表达基因。本研究比较了RIF和RM患者在着床窗口期的子宫内膜转录组;确定了RIF和RM子宫内膜中潜在影响着床过程的差异分子途径。