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

Abstract

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.

Transcriptomic profiles in peripheral blood between women with unexplained recurrent implantation failure and recurrent miscarriage and the correlation with endometrium: A pilot study

“…Previous studies had successfully used transcriptomic profiles of the endometrium to characterize different groups of women with reproductive failure (RIF [ 7 – 9 , 31 , 32 ] or RM [ 10 – 12 ]); our observation suggested that it was not possible to do so with transcriptomic profile of the peripheral blood. It raises questions about the possible clinical usefulness of the peripheral blood to monitor the molecular changes in the endometrium in the window of implantation.…”

“…The unsupervised hierarchical clustering and PCA were done as previously described [ 12 ]. Briefly, the raw normalized expression of genes were scaled and used for unsupervised hierarchical clustering and PCA by R packages gplots [ 19 ] and prcomp.…”

“…Several studies have used this approach to examine the endometrium in the peri-implantation period of women with recurrent implantation failure (RIF) [ 7 – 9 ] or recurrent miscarriage (RM) [ 10 , 11 ]. Our previous study has found different pathway regulations between RIF and RM [ 12 ]. Furthermore, whole blood transcriptome studies could reveal other physical changes of human body, like blood pressure [ 13 ], pre-term labor [ 14 ], or immune response [ 15 ].…”

Ultrasound-guided embryo transfer: summary of the evidence and new perspectives. A systematic review and meta-analysis

“…Over the past decade, despite great improvement in IVF settings and treatments, embryo implantation and related mechanisms are not well understood (Abou-Setta et al, 2007). Several factors can affect embryo implantation, but the actual trend is to focus specifically on the embryo (Huang et al, 2017), leaving aside the fundamental role of endometrial receptivity (Edwards, 1995;Hoozemans et al, 2004;Irani et al, 2017) and the possible improvement derived by different embryo transfer techniques (Tang et al, 2001). Indeed, the transfer of a goodquality euploid embryo does not ensure a successful implantation or an ongoing pregnancy (Teh et al, 2016).…”

Exosomal microRNAs as potential biomarkers for cancer cell migration and prognosis in hepatocellular carcinoma patient-derived cell models

“…The expression levels were normalized using DESeq2 version 1.20.0. The principal component analysis (PCA) and the contribution of each gene to the dominant direction were performed as described by Huang et al ( 13 ). miRNAs that met all the following conditions were considered differentially expressed: i) P<0.05 between two groups; ii) the absolute value of contribution was >0.03; and iii) the average expression level of groups with higher mean expression was >100 reads per kilobase per million mapped reads (RPKM).…”