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SIRT3 ameliorates polycystic ovary syndrome through FOXO1/PGC-1α signaling pathway

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Abstract

Background

Current studies have shown that Sirtuin3 (SIRT3) plays a key role in oocyte maturation. Polycystic ovary syndrome (PCOS) is a common disease caused by endocrine and metabolic abnormalities. The specific regulatory role and mechanism of SIRT3 in PCOS have not been reported.

Methods

SIRT3 was overexpressed in dihydrotestosterone (DHT)-induced PCOS model in mice. Ovary morphology, serum hormone level, and apoptosis of tissue cells were detected. The expression of SIRT3/Forkhead box protein O1 (FOXO1)/peroxlsome proliferator-activated receptor-γ coactlvat-1α (PGC-1α)-related proteins was detected. Then SIRT3 was overexpressed in DHT-induced human granulosa-like tumor cell line KGN. After the detection of the pathway-associated proteins, PGC-1α specific inhibitor SR-18292 was added to detect cell apoptosis, mitochondrial membrane potential, mitochondrial ROS (MitoROS) levels, and other mitochondrial-related indicators

Results

The expression of SIRT3 in PCOS model was significantly decreased. Overexpression of SIRT3 could significantly improve ovarian morphology and serum sex hormone levels in DHT-induced PCOS mice and inhibit apoptosis both in vitro and in vivo. Overexpression of SIRT3 also could improve mitochondrial dysfunction in DHT-induced KGN cells via FOXO1/PGC-1α signaling pathway. And PGC-1α inhibitor SR-18292 reversed the protective effect of SIRT3 overexpression on apoptosis and mitochondrial function damage of DHT-induced KGN cells.

Conclusion

SIRT3 regulated FOXO1/PGC-1α signaling pathway to reduce mitochondrial dysfunction in PCOS, thereby improving PCOS.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Funding

This study was supported by The Natural Science Foundation of Hubei Province of China (2022CFC023; 2021CFB093) and Medical Science and Technology Innovation Platform Support Project of Zhongnan Hospital, Wuhan University (PTXM2023030).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China

    Xiaomeng Pang, Jing Cheng, Tiancheng Wu & Lili Sun

Authors
  1. Xiaomeng Pang
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  2. Jing Cheng
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  3. Tiancheng Wu
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  4. Lili Sun
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Contributions

Lili Sun and Xiaomeng Pang wrote the manuscript and analyzed the data. Jing Cheng, Tiancheng Wu and Lili Sun performed the experiments and supervised the study. Jing Cheng and Tiancheng Wu searched the literature and revised the manuscript for important intellectual content. Lili Sun and Xiaomeng Pang confirm the authenticity of all the raw data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lili Sun.

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The authors declare no competing interests.

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All the authors agreed to be published.

Ethics approval and consent to participate

All animal procedures were operated according with the NIH Guide for the Care and Use of Laboratory Animals approved by the ethical guidelines of Zhongnan Hospital of Wuhan University.

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Pang, X., Cheng, J., Wu, T. et al. SIRT3 ameliorates polycystic ovary syndrome through FOXO1/PGC-1α signaling pathway. Endocrine 80, 201–211 (2023). https://doi.org/10.1007/s12020-022-03262-x

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  • DOI: https://doi.org/10.1007/s12020-022-03262-x

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