Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers

Abstract

Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up- and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from ‘pre-receptive’ and 88 from mid-secretory, ‘receptive’ phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.

Application of ultrasound multimodal score in the assessment of endometrial receptivity in patients with artificial abortion

“…No endometrium peristalsis wave within 3 min; score, 1; c two-dimensional gray-scale mode; endometrial thickness, 6.0 mm; score, 1; endometrial type, type C; score, 1; d 2D color Doppler mode; a little blood flow in the subendometrium; score, 2; e threedimensional mode; EV, 1.56 cm 3 ; score, 1; f three-dimensional mode; VFI, 0.027; score, 2 assessment of endometrial repair, but these features have limitations in the monitoring of disease condition and the diagnosis and treatment of diseases. In recent years, increasing attention has been paid to the role of recovery of endometrial receptivity in the endometrial repair [4,[14][15][16]. Although many studies have been conducted to investigate the endometrial receptivity, the methods in these studies are often different and there are no widely accepted criteria for the assessment of endometrial receptivity.…”

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing

“…We identified ITGB4 as a unique marker of trophoblast cells. LAMB3 , which plays an important role in the endometrial extracellular matrix during early pregnancy [33], may be signaling trophoblasts through ITGB4 and mediating invasion into maternal tissue during placentation, and needs to be studied further.…”

Lipidomic profile as a noninvasive tool to predict endometrial receptivity

“…Of the hundreds of gene expression changes typically identified by microarray, relatively few are common to more than two studies (Haouzi, Dechaud, Assou, De Vos, & Hamamah, ; Horcajadas et al, ). Although the metasignature of endometrial receptivity has recently been described (Altmae et al, ), comparisons of proteomic data with published gene expression data in similar cohorts of women (Burney et al, ; Chen et al, ; Haouzi et al, ) have also revealed an overall lack of correlation between the two, suggesting that posttranscriptional or translational regulation is an important feature of endometrial remodeling.…”