Mechanism of resveratrol in improving ovarian function in a rat model of premature ovarian insufficiency

• Published in: The journal of obstetrics and gynaecology research Vol. 44; no. 8; pp. 1431 - 1438
• Main Authors: Li, Ning, Liu, Lili
• Format: Journal Article
• Language: English
• Published: Kyoto, Japan John Wiley & Sons Australia, Ltd 01.08.2018; Wiley Subscription Services, Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Antioxidants - administration & dosage; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Caspase; Disease Models, Animal; Female; Granulosa cells; Granulosa Cells - drug effects; Immunohistochemistry; Malondialdehyde; Oral administration; Ovary - drug effects; Ovary - metabolism; Oxidative stress; Oxidative Stress - drug effects; PI3K/Akt/mTOR signaling pathway; Pregnancy; premature ovarian insufficiency; Primary Ovarian Insufficiency - blood; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - drug therapy; Primary Ovarian Insufficiency - metabolism; rat; Rats; Rats, Sprague-Dawley; Resveratrol; Resveratrol - administration & dosage; Resveratrol - pharmacology; Rodents; Serum levels; Signal transduction; Signal Transduction - drug effects; Superoxide dismutase; TOR protein; PI3K/Akt/mTOR signaling pathway; premature ovarian insufficiency; rat; resveratrol
• ISSN: 1341-8076; 1447-0756
• DOI: 10.1111/jog.13680

Aim To investigate the mechanism of resveratrol treatment in chemically induced premature ovarian insufficiency (POI) in rats. Methods Five‐week‐old specific pathogen‐free healthy Sprague–Dawley female rats (n = 90) were randomly divided into five groups (n = 18): low‐dose resveratrol (group A), moderate‐dose resveratrol (group B), high‐dose resveratrol (group C), model control group (group D) and blank control group (group E). POI was induced in rats from the resveratrol‐treated groups and the model control group according to observed indexes using a previously established model (oral administration of tripterygium wilfordii polyglycoside tablet 50 mg/kg/day for 14 days). Western blot analysis was performed to compare levels of PI3K, p‐PI3K, Akt, p‐Akt, mTOR, p‐mTOR, Bax, Bcl‐2 and Caspase‐3 in ovarian tissues of each group, and expression of p‐Akt, p‐mTOR, Bax, Bcl‐2 and Caspase‐3 was also evaluated by immunohistochemistry. Serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined using enzyme‐linked immunosorbent assay. Results Compared with controls, we found that serum MDA decreased and SOD increased in resveratrol‐treated groups. In addition, we found increased expression of p‐PI3K, p‐Akt, p‐mTOR and Bcl‐2, and decreased expression of Bax and Caspase‐3 were observed in ovarian tissues of treated rats with POI. There was reduced ovarian function in POI rats compared with rats from the blank control group. Conclusion Resveratrol reduced oxidative stress and inhibited apoptosis in granulosa cells by activating the PI3K/Akt/mTOR signaling pathway in a rat model of POI.