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

by Selleckchem | Aug 09 2023

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.

Comments:

The research study you mentioned investigates the role of Sirtuin3 (SIRT3) in polycystic ovary syndrome (PCOS). PCOS is a common endocrine disorder characterized by hormonal imbalances and metabolic abnormalities. The specific regulatory role and mechanism of SIRT3 in PCOS have not been previously reported. The study used both animal and cell culture models to explore the effects of SIRT3 on PCOS and its underlying mechanisms.

In the animal model, the researchers induced PCOS in mice by administering dihydrotestosterone (DHT), a hormone associated with PCOS. They then overexpressed SIRT3 in these mice and examined the effects on ovarian morphology, serum hormone levels, and tissue cell apoptosis. The expression of SIRT3 and other related proteins, including Forkhead box protein O1 (FOXO1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), was also measured.

The results showed that the expression of SIRT3 was significantly decreased in the PCOS model. However, overexpression of SIRT3 improved ovarian morphology, normalized serum sex hormone levels, and reduced apoptosis in both in vitro and in vivo settings. This suggests that SIRT3 has a protective effect on PCOS.

To further investigate the underlying mechanisms, the researchers used a human granulosa-like tumor cell line called KGN. They induced PCOS-like conditions in these cells using DHT and then overexpressed SIRT3. The expression of proteins associated with the FOXO1/PGC-1α signaling pathway was measured. Additionally, they added a specific inhibitor of PGC-1α called SR-18292 to assess its effects on cell apoptosis, mitochondrial membrane potential, and mitochondrial reactive oxygen species (ROS) levels, as well as other mitochondrial-related indicators.

The findings demonstrated that overexpression of SIRT3 improved mitochondrial dysfunction in the DHT-induced PCOS cells through the FOXO1/PGC-1α signaling pathway. Furthermore, the addition of the PGC-1α inhibitor reversed the protective effects of SIRT3 overexpression on apoptosis and mitochondrial function damage in the PCOS cells.

In conclusion, this study suggests that SIRT3 plays a regulatory role in PCOS by modulating the FOXO1/PGC-1α signaling pathway. By reducing mitochondrial dysfunction, SIRT3 improves the condition of PCOS. These findings contribute to a better understanding of the molecular mechanisms underlying PCOS and may offer potential therapeutic targets for the treatment of this syndrome.