BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2020-08, Vol.19 (15), p.1884-1898
• Main Authors: Gao, Tingting, Lin, Meng, Shao, Binbin, Zhou, Qiao, Wang, Yufeng, Chen, Xia, Zhao, Dan, Dai, Xiuliang, Shen, Cong, Cheng, Hongbo, Yang, Shenmin, Li, Hong, Zheng, Bo, Zhong, Xingming, Yu, Jun, Chen, Li, Huang, Xiaoyan
• Format: Article
• Language: English
• Subjects: BMI1; Leydig cells; oxidative stress; p16/p19 signaling; Research Paper; steroidogenesis
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2020.1779471

In males, aging is accompanied by decline in serum testosterone levels due to impairment of testicular Leydig cells. The polycomb protein BMI1 has recently been identified as an anti-aging factor. In our previous study, BMI1 null mice showed decreased serum testosterone and Leydig cell population, excessive oxidative stress and p16/p19 signaling activation. However, a cause-and-effect relationship between phenotypes and pathways was not investigated. Here, we used the rescue approach to study the role of oxidative stress or p16/p19 in BMI1-mediated steroidogenesis. Our results revealed that treatment with antioxidant NAC, but not down-regulation of p16/p19, largely rescued cell senescence, DNA damage and steroidogenesis in BMI1-deficient mouse MLTC-1 and primary Leydig cells. Collectively, our study demonstrates that BMI1 orchestrates steroidogenesis mainly through maintaining redox homeostasis, and thus, BMI1 may be a novel and potential therapeutic target for treatment of hypogonadism.