The aim of this study was to investigate the effect and mechanism of action of miR-1298-5p in polycystic ovary syndrome (PCOS). Granulosa cells were isolated from follicular fluid of patients with PCOS and healthy women, and the expression of miR-1298-5p and glutathione-disulfide reductase (GSR) mRNA in these cells was evaluated using reverse transcription-quantitative polymerase chain reaction (qRT-PCR). Clinical data were obtained from all subjects, and reproductive hormones and endocrine indices were assayed to analyze the correlation between miR-1298-5p and clinicopathological characteristics of patients with PCOS. Following transfection with the miR-1298-5p mimic or inhibitor and/or pcDNA3.1-GSR, LC3 immunofluorescence and transmission electron microscopy were used to evaluate autophagy in the COV434 human granulosa cell line. Additionally, western blotting was performed to detect LC3-II, Beclin 1, and p62 protein levels in COV434 cells. The interaction between miR-1298-5p and GSR was also examined. A PCOS rat model was established and injected with the miR-1298-5p antagomir, followed by measurement of body and ovary weights, histological examination, and autophagosome observation. The protein expression levels of GSR, LC3-II, Beclin 1, and p62 were determined in rat ovaries. miR-1298-5p was expressed at a high level, and GSR was downregulated in granulosa cells from patients with PCOS. In COV434 cells, miR-1298-5p inversely mediated GSR expression, and miR-1298-5p mimic transfection promoted autophagy, whereas GSR overexpression blocked miR-1298-5p mimic-promoted autophagy. In PCOS rats, miR-1298-5p inhibition reduced autophagy and alleviated abnormalities in follicular development. Overall, miR-1298-5p enhances autophagy in granulosa cells by downregulating GSR, thereby affecting PCOS development.
Keywords: Autophagy; Glutathione-disulfide reductase; Granulosa cell; Polycystic ovary syndrome; miR-1298-5p.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.