Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization

摘要

Abstract Problem DNA methylation profile in mid‐secretory phase of endometrium is reported to be varied from other phases in natural menstrual cycle. Therefore, we intended to study the impairment in endometrial receptivity by performing whole‐genome methylation and gene expression profiling in endometrium of recurrent implantation failure patients (RIF) during IVF under controlled ovarian stimulation (COS). Method of study Endometrial biopsies were collected from IVF‐RIF patients (cases, n?=?6) and healthy fertile oocyte donors (controls, n?=?6) undergoing COS after 6/7th day of human chorionic gonadotropin administration. The whole‐genome methylation and gene expression microarray were performed and analysed by GenomeStudio software ( P ??.05 by Illumina Custom Model), whereas the enrichment analysis was performed using “Database for Annotation, Visualization and Integrated Discovery” (DAVID, V6.8). Significant differentially methylated genes were correlated with dys‐regulated genes using Pearson's correlation. Results Differential methylation in RIF patients revealed 448 CpG sites. The enrichment analysis showed aberrant methylation in genes involved in immunological response and G protein activity. Methylation in NLRP2 gene in inflammatory pathway had significant negative correlation with gene expression ( P ?=?.008), whereas SERPINA5 gene that is already known to be involved in endometrial receptivity was observed to be hypomethylated in promoter region with highest delta beta value and up‐regulated in gene expression analysis. Conclusion The aberrant methylation of genes involved in immunological functions and G protein activation was found to be prevalent which might suggest a role in endometrial receptivity. However, the findings need to be further validated on a larger cohort of IVF‐RIF patients.