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

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.

Keywords: FOXO1/PGC-1α signaling pathway; Mitochondrial function; Polycystic ovary syndrome; SIRT3.