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MicroRNA-1298-5p in granulosa cells facilitates cell autophagy in polycystic ovary syndrome by suppressing glutathione-disulfide reductase

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Abstract

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.

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Availability of data and materials

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Thanks for all the contributors and participants.

Funding

This research was funded by the grants from the National Natural Science Foundation of China (No. 81670004; No. 32072738); Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research Fund; Guangxi Natural Science Fund Project (No. 2017GXNSFAA198163); Nanning Scientific Research and Technology Development Program (No.20213024); Guangxi National Natural Science Foundation (No. 2020GXNSFAA159099); Nanning Qingxiu District Science and Technology Project (No. 2020025); Nanning Jiangnan District Project (No. 202001206); and Key R & D Program of Scientific Research and Technology of Nanning Liangqing District (No. 202009).

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Authors and Affiliations

  1. The Reproductive Medical Center, Nanning Second People’s Hospital, No.13 Dancun Road, Nanning, Guangxi 530031, People’s Republic of China

    Changlong Xu

  2. College of Animal Science and Veterinary, Shandong Agricultural University, Tai’an, Shandong 271018, People’s Republic of China

    Mingjiu Luo

  3. Department of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, No. 6699, Qingdao Road, Huaiyin District, Jinan, Shandong, 250000, People’s Republic of China

    Xiaodong Liu, Tao Wei, Zheng Zhou, Changze Li, Zilin He & Hongshu Sui

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  1. Changlong Xu
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Contributions

XCL and SHS conceived the ideas. SHS, XCL, and LMJ designed the experiments. LMJ, LXD, WT, and ZZ performed the experiments. LCZ and HZL analyzed the data. LMJ, LXD, and WT provided critical materials. ZZ and LCZ wrote the manuscript. SHS supervised the study. All the authors have read and approved the final version for publication.

Corresponding author

Correspondence to Hongshu Sui.

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Ethical approval and consent to participate

The study protocol was approved by the ethic committee of Shandong First Medical University. Written informed consent was obtained from each patient participated in this study prior to study enrollment. Efforts were made as much as possible to minimize the pain of animals.

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The author declares no competing interests.

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Xu, C., Luo, M., Liu, X. et al. MicroRNA-1298-5p in granulosa cells facilitates cell autophagy in polycystic ovary syndrome by suppressing glutathione-disulfide reductase. Cell Tissue Res 392, 763–778 (2023). https://doi.org/10.1007/s00441-023-03747-9

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