Integrated miRNA-seq analysis reveals the molecular mechanism underlying the effect of acupuncture on endometrial receptivity in patients undergoing fertilization - embryo transplantation

Endometrial receptivity (ER) is the main factor affecting in vitro fertilization (IVF) and embryo transplantation. Previous studies have shown that acupuncture might be useful for increasing ER. However, the underlying molecular mechanisms deserve to be further elucidated.In this study, we performed small RNA sequencing of endometrial samples from infertile women who either underwent acupuncture therapy or did not. Differentially expressed micro RNAs (miRNAs) were identified, and their target-genes were predicted. Moreover, the function and signaling pathway were analyzed for expression of the target genes. In addition, Real-time PCR was performed to validate the RNA-seq results. We identified 39 differentially expressed miRNAs (DEmiRNAs), and predicted their target genes in the acupuncture group compared with those in the control group. The functional enrichment analysis suggested that the target genes of the DEmiRNAs were significantly enriched in GO-BP terms associated with transcription, such as regulation of DNA-templated transcription and positive regulation of DNA-templated transcription. The pathway analysis showed that DEmiRNAs might be involved in acupuncture therapy via Endocytosis, Axon guidance, Oxytocin signaling, the Hippo pathway, and Estrogen signaling pathways. Downregulation of hsa-miR-449a and hsa-miR-449b-3p, and up-regulation of hsa-miR-3135b and hsa-miR-345-3p in the RNA-seq results were validated by Real-time PCR. Our results predict possible mechanisms by which acupuncture therapy might help increase ER and promote endometrium receptivity in preparation for in vitro fertilization and embryo transplantation.