Genome-Wide Profiling of Long Noncoding RNA Expression Patterns in Women With Repeated Implantation Failure by RNA Sequencing

Abstract

Objectives: To compare long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression levels in endometrium between patients with repeated implantation failure (RIF) following in vitro fertilization (IVF)-embryo transfer and control women.

Materials and methods: RNA sequencing (RNA-seq) and alignments were performed to identify lncRNAs and mRNAs using endometrial samples collected from 3 patients and 3 control women. A subset of 10 differentially expressed lncRNAs and 6 mRNAs were validated in all participants using quantitative reverse transcription polymerase chain reaction. The potential biological roles of identified lncRNAs were predicted via coexpressed mRNA annotations. Twenty patients with RIF and 30 control women were recruited for validation.

Results: We identified 1202 differentially expressed genes, including 742 lncRNAs and 460 mRNAs, in mid-secretory phase endometrial tissue from patients with RIF following IVF compared to control women. We analyzed the target genes of the lncRNAs and uncovered 148 lncRNAs corresponding to 147 cis-regulated target genes. The cis-regulated target genes of these significantly differentially expressed lncRNAs were clustered into several pathways, such as the tumor necrosis factor signaling pathway, the Toll-like receptor signaling pathway, and the NF-kappa B (NF-κB) signaling pathway.

Conclusion: Our study constitutes the first report on the investigation of the regulatory mechanisms of lncRNAs in endometrial receptivity in women experiencing RIF using RNA-seq. Our results provide a valuable candidate reservoir for future functional studies of lncRNAs.

Keywords: RNA sequencing; long noncoding RNA; repeated implantation failure.