Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT/ERK signalling pathway

BMC Women's Health

Research

Na Sun¹  Lilan Sun¹  Yuemin Zhang¹  Huagang Ma¹  Jinguang Wang¹  Pingping Sun¹ 

[1] Reproductive Medicine Center, Weifang People’s Hospital, No. 151, Guangwen Street, Kuiwen District, 261000, Weifang, Shandong, China;

关键词: Kisspeptin;    Polycystic ovary syndrome;    Granulosa cell;    Oxidative stress;    Apoptosis;    PI3K/AKT/ERK signalling;   

DOI  :  10.1186/s12905-022-02154-6

 received in 2022-07-14, accepted in 2022-12-30,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe development of polycystic ovary syndrome (PCOS) is closely correlated with apoptosis and oxidative stress in ovarian granulosa cells. Kisspeptin plays an important role in reproductive organ function. This study aimed to explore the role of kisspeptin in PCOS and oxidative stress-triggered apoptosis of ovarian granular cells.MethodsA PCOS rat model was established by injecting dehydroepiandrosterone (DHEA) and feeding the rats a high-fat diet. The RNA and protein levels of kisspeptin were analysed by quantitative PCR, western blotting, and histological staining. Tissue damage was evaluated using haematoxylin and eosin (H&E) staining. The viability and proliferation of human granulosa cell KGN were measured using the cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays. Cell cycle and apoptosis were analysed by flow cytometry. Oxidative stress was analysed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels.ResultsKisspeptin was downregulated in the ovarian granulosa cells of PCOS rats compared to those of control rats. Kisspeptin overexpression enhanced KGN cell proliferation and inhibited apoptosis. ROS generation was suppressed by kisspeptin, along with decreased levels of MDA and increased levels of the antioxidants GSH, SOD, and CAT. Kisspeptin activates PI3K/AKT and ERK signalling, and inactivation of ERK1/2 suppresses the protective role of kisspeptin in ovarian granulosa cells.ConclusionKisspeptin improves proliferation and alleviates apoptosis and oxidative stress in ovarian granulosa cells by activating PI3K/AKT and ERK signalling.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2022_35_Article_IEq173.gif

Fig. 5

41116_2022_35_Article_IEq159.gif

41116_2022_35_Article_IEq147.gif

41116_2022_35_Article_IEq135.gif

41116_2022_35_Article_IEq125.gif