The Effect of Acupuncture on MiRNA Expression Profiles in the Ovaries of Rats with PCOS and Insulin Resistance

Abstract

Background: Polycystic ovary syndrome (PCOS) is one of the most commonendocrine and metabolic diseases of women of reproductive age. The majorcharacteristics of PCOS are anovulation, hyperandrogenism, infertility, and insulinresistance. Previous studies showed that acupuncture could promote menstruation,decrease testosterone levels, increase insulin sensitivity, and improve frequency ofovulation in women with PCOS. However, the mechanism of how acupunctureregulates the reproductive and metabolic abnormalities of PCOS remains unclear. Thepresent study investigated the differential expression of miRNAs in the ovaries of ratswith PCOS and insulin resistance (IR) after electroacupuncture (EA) treatment.Methods: A rat model of PCOS with IR was established by letrozole and a high-fatdiet. Rats in the PCOS+EA group received acupuncture treatment five times a week forfour weeks. The differentially expressed miRNAs of three rat ovaries of each group(n=3/group) were identified by deep sequencing. The differentially expressed miRNAsare shown by a hierarchical clustering heatmap and volcano plot. Gene ontology (GO)analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysiswere conducted to explore the potential target genes of the differentially expressedmiRNAs and identify their putative biological function. Eight of the differentiallyexpressed miRNAs were selected for validation by real-time quantitative PCR (qRTPCR).Results: The rats in the PCOS+EA group had significantly decreased body weight andincreased insulin sensitivity compared with the rats in the PCOS group. EA tend toreduce testosterone levels in the rats with PCOS and insulin resistance. The rats in thePCOS+EA group displayed fewer large cystic follicles, fewer atretic antral follicles,and more corpora lutea than the rats in the PCOS group. A total of 23 differentiallyexpressed miRNAs were identified in the PCOS with IR group after EA treatment,including 15 miRNAs that were upregulated and 8 miRNAs that were downregulated.GO and KEGG pathway analyses indicated that the predicted target genes were relatedto cellular processes, and metabolic pathways. Furthermore, qRT-PCR confirmed thatmiRNA-181 was significantly downregulated in the rat ovaries of the PCOS+EA groupcompared with the PCOS group.Conclusion: Our results indicate that differentially expressed miRNAs may mediate the effect of acupuncture on insulin sensitivity in PCOS with IR. It will be beneficial to study the mechanism of acupuncture in improving insulin resistance in women with PCOS.