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Updated: Aug 15, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
SIRT3 ameliorates polycystic ovary syndrome through FOXO1/PGC-1α signaling pathway
Xiaomeng Pang1, Jing Cheng1, Tiancheng Wu1
1Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
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.
Insights
Sirtuin3 (SIRT3) overexpression improves polycystic ovary syndrome (PCOS) by regulating mitochondrial function via the FOXO1/PGC-1α pathway. This finding offers a potential therapeutic target for PCOS treatment.
Area of Science:
- Endocrinology
- Metabolic Research
- Cell Biology
Background:
- Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder.
- Sirtuin3 (SIRT3) is implicated in oocyte maturation, but its role in PCOS remains unclear.
Purpose of the Study:
- To investigate the regulatory role and mechanism of SIRT3 in PCOS.
- To explore SIRT3's impact on mitochondrial function and related pathways in PCOS models.
Main Methods:
- Overexpression of SIRT3 in dihydrotestosterone (DHT)-induced PCOS mouse models and human granulosa-like tumor cells (KGN).
- Assessment of ovarian morphology, serum hormone levels, apoptosis, and mitochondrial function (mitochondrial membrane potential, MitoROS).
- Analysis of the SIRT3/Forkhead box protein O1 (FOXO1)/peroxlsome proliferator-activated receptor-γ coactlvat-1α (PGC-1α) signaling pathway.
Main Results:
- SIRT3 expression was decreased in PCOS models.
- SIRT3 overexpression ameliorated ovarian morphology, normalized hormone levels, and reduced apoptosis in PCOS mice.
- SIRT3 overexpression improved mitochondrial dysfunction in KGN cells via the FOXO1/PGC-1α pathway, an effect reversed by a PGC-1α inhibitor.
Conclusions:
- SIRT3 plays a protective role in PCOS by mitigating mitochondrial dysfunction.
- The SIRT3/FOXO1/PGC-1α pathway is a key mechanism through which SIRT3 exerts its beneficial effects in PCOS.
- Targeting SIRT3 may represent a novel therapeutic strategy for PCOS.
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