Integrative Bioinformatics Analysis of Endometrial Transcriptome Reveals Key Regulatory Networks in Recurrent Implantation Failure

Recurrent implantation failure (RIF) is a serious clinical dilemma which occurs in assisted reproductive technologies (ART) in women who are unable to conceive after multiple embryo transfer. RIF molecular mechanisms should be elucidated in order to pursue advancement in ART.This study introduced an integrative bioinformatics approach to study publicly available RNA-Seq data with a specific focus on the endometrial transcriptome of patients with RIF.Two hundred differentially expressed genes (DEGs) were identified and characterized. Out of which, ۱۱۲ genes were up regulated and ۸۰ genes were down regulated in RIF patients compared to controls. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed significant involvement of biological pathways in processes related to remodeling of the extracellular matrix (ECM), immune response and angiogenesis. Similarly, there was a significant involvement of molecular signalling pathways such as the PI۳K-Akt signalling pathway and MAPK signalling pathway, which contribute to the overall pathophysiology of RIF. In addition, protein-protein interaction (PPI) network analysis showed several hub genes and functional genes (pathogen nexus) that are important for regulation of cell adhesion, extracellular matrix (ECM) remodeling and angiogenesis, which were identified as ITGB۳, MMP۹, VEGF and FN۱. Gene regulatory network (GRN) models showed several core transcriptional factors, for example NF-kB, TP۵۳ and HIF۱A, that regulate the fundamental mechanisms in each domain. Overall, this study provides new insights into the molecular bases underlying RIF and will help profile new biomarkers and therapeutic targets to support a successful pregnancy.

کلیدواژه ها:

Recurrent Implantation Failure ، Endometrial Transcriptome ، RNA-Seq ، Differentially Expressed Genes