Abstract
BackgroundPrevious work demonstrated that there are numerous miRNAs in human follicular fluids, some of which are associated with reproductive diseases. In the current study, we sought to determine whether microRNAs (miRNAs) in the follicular fluid (FF) are differentially expressed between women with and without endometriosis and to uncover the association of miRNAs with the oocyte and embryonic development potential.MethodsFF was harvested from 30 women with endometriosis and 30 women without who underwent in vitro fertilization treatment at the University Hospital between February and December 2016. The FF samples were subjected to miRNA profiling and validation via quantitative reverse transcription polymerase chain reaction analysis. Mouse/human metaphase-I (MI) oocytes were harvested and micro-injected with an miR-451 inhibitor, and the effects of miR-451 knockdown on Wnt/WNT signalling genes were investigated.ResultsOocyte number, fertilization rate, and number of available embryos were decreased significantly in women with endometriosis relative to those without endometriosis. Hsa-miR-451 in FF was downregulated in endometriosis patients relative to control subjects (P < 0.01). Moreover, the proportions of mouse/human MI oocytes that developed into 2-pronuclei (2PN), 2-cell, 8–10-cell and blastocyst-stage embryos were affected by miR-451 knockdown in mouse/human oocytes. Components of the Wnt signalling pathway were aberrantly expressed in the mouse/human oocytes and embryos in the miR-451 inhibitor-injected group.ConclusionsmiR-451 was downregulated in FF samples from endometriosis patients and was modestly effective in distinguishing endometriosis patients from non-endometriosis patients. miR-451 downregulation in mouse and human oocytes affected pre-implantation embryogenesis by suppressing the Wnt signalling pathway. This miRNA might serve as a novel biomarker of oocyte and embryo quality in assisted reproductive treatment.
Highlights
Endometriosis is a common oestrogen-related gynaecological disorder that is known to cause serious pelvic pain and infertility and affects 6–10% of reproductiveaged women and 20–50% of infertile women [1, 2]
The two groups did not differ in age, years of infertility, body mass index (BMI), cycle length, endometrial thickness, proportion of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), or hormone levels
follicular fluid (FF) miRNAs in endometriosis group with Raw Ct (miRNA) profiles and the identification of differentially expressed miRNAs in participants with and without endometriosis The finding that embryo quality was higher in the control group than in the endometriosis group suggested
Summary
Endometriosis is a common oestrogen-related gynaecological disorder that is known to cause serious pelvic pain and infertility and affects 6–10% of reproductiveaged women and 20–50% of infertile women [1, 2]. MicroRNAs (miRNAs) are highly conserved, singlestranded, non-coding RNA molecules comprising 20–24 nucleotides. They regulate gene expression, primarily at the posttranscriptional level, through various mechanisms, with positive or negative effects [5, 6]. Recent studies have reported that the miRNA expression profiles of human FF can be used to distinguish high-quality embryos from low-quality ones [8] and affect pathways of ovarian function and follicle development [9]. We sought to determine whether microRNAs (miRNAs) in the follicular fluid (FF) are differentially expressed between women with and without endometriosis and to uncover the association of miRNAs with the oocyte and embryonic development potential
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