Protective Effect of SCUBE1 on Oxidative Stress-induced Apoptosis in Human Ovarian Granulosa Cells

Abstract Background: Apoptosis of ovarian granulosa cells (GCs) is a sign of follicular atresia. This study aimed to explore the role and mechanism of signal peptide, CUB domain, epidermal growth factor-like protein1 (SCUBE1) in protecting GCs from apoptosis induced by hydrogen peroxide (H2O2). Results: SCUBE1 was expressed in women of all ages and had the highest expression level in the ovaries in multiple organs and tissues of KM mouse. In vitro cell experiments show that SCUBE1 pretreatment reduced H2O2-induced apoptosis and improved cell viability. SCUBE1 also blocked the production of ROS in cells and improved mitochondrial membrane potential. After SCUBE1 pretreatment, anti-apoptotic protein Bcl-2 expression was upregulated, whereas the expression of the pro-apoptotic proteins Bax, Bax/Bcl-2, Caspase-3, and p53 were downregulated. Analysis of the impact of SCUBE1 (c.1169C >G, p.P390R) mutation from the aspect of mutation pathogenicity; protein stability; and gene haplotype insufficiency, indicated that the p.P390R mutation is significantly pathogenic. Conclusions: This is the first time that the potential role of SCUBE1 in protecting GCs from H2O2-induced damage by blocking the production of ROS, increasing the mitochondrial membrane potential and regulating apoptosis-related proteins, attributing to POI, is studied. SCUBE1 (c.1169C >G, p.P390R) mutation has significant pathogenicity but the specific harm needs to be confirmed by further studies.