Extracellular vesicles-derived MicroRNA-145-5p is upregulated in the uterine fluid of women with endometriosis and impedes mouse and human blastocyst development.

Abstract

Previous work indicated that the implantation and pregnancy rates of women with endometriosis are lower than those of healthy women during in-vitro fertilisation and embryonic transfer. And there are numerous microRNAs (miRNAs) in human uterine luminal fluid (ULF), some of which are associated with early preimplantation development of embryos. In our study, we sought to determine whether miRNAs in the ULF are differentially expressed between women with and without endometriosis and to uncover the association of miRNAs with the development potential of blastocysts. The implantation and clinical pregnancy rates significantly decreased in women with endometriosis than in those without endometriosis. Notably, hsa-miR-145-5p was upregulated in ULF samples from women with endometriosis (fold change > 2, false discovery rate < 0.001). Moreover, the ratios of mouse/human early embryos that developed into blastocyst-staged embryos (P = 0.0065 and P = 0.0098, respectively) were significantly affected via miR-145-5p upregulation in mouse/human early embryos. Notch signalling pathway components had abnormal expression levels in the mouse/human blastocyst-stage embryos in the miR-145-5p mimic-enriched extracellular vesicles (EVs) group. In conclusions, our study revealed that human extracellular vesicle-derived miRNAs in ULF impacted the developmental potential of blastocysts in women with endometriosis. Moreover, the upregulation of miR-145-5p-enriched EVs in mouse and human embryos negatively affected blastocyst development by suppressing the expression of components of the NOTCH signalling pathway, which may contribute to elucidate the cause of infertility in women with endometriosis.