Differential expression of microRNA in exosomes derived from endometrial stromal cells of women with endometriosis-associated infertility

Research question: What is the expression pattern of microRNA (miRNA) in exosomes isolated from eutopic endometrial stromal cells (EuESC) of women with endometriosis-associated infertility? Design: Small RNA sequencing was conducted in exosomes isolated from EuESC of women with endometriosisassociated infertility (n = 3) and normal endometrial stromal cells (NESC) of fertile women without endometriosis (n = 3). The differentially expressed miRNA in exosomes derived from EuESC and NESC were identified. The functions of the differentially expressed miRNA were analysed by gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Small RNA sequencing showed that the percentages of exosomal miRNA in the total small RNA isolated from EuESC and NESC were not significantly different (P = 0.7804). A total of 49 differentially expressed miRNA (fold change >1.5 and P < 0.05) were identified, including 26 up-regulated and 23 down-regulated in EuESC exosomes as compared with NESC exosomes. Functional analysis revealed that 12 miRNA were predicted to target homeobox A10 (HOXA10) and/or the leukaemia inhibitory factor (LIF) 3' untranslated region (UTR). Both HOXA10 and LIF mRNA expression levels were significantly decreased in EuESC compared with NESC (P = 0.0222 and 0.0395, respectively). In addition, the predicated target genes of these differentially expressed exosomal miRNA were significantly (P < 0.05) enriched in 76 pathways, including the MAPK and Wnt signalling pathways. Conclusions: The differential expression patterns of exosomal miRNA were identified. Many exosomal miRNA may be involved in regulating the endometrial receptivity of women with endometriosis-associated infertility.