Obesity-induced inflammatory miR-133a mediates apoptosis of granulosa cells and causes abnormal folliculogenesis Role of miR-133a in folliculogenesis

• Published in: Acta biochimica et biophysica Sinica Vol. 55; no. 8; pp. 1234 - 1246
• Main Authors: Chen, Ruizhi, Wu, Xueqing, Qiu, Han, Yang, Baiming, Chen, Yao, Chen, Xiang, Li, Yingshan, Yuan, Shaochun, Liu, Dan, Xiao, Luanjuan, Yu, Yanhong
• Format: Journal Article
• Language: English
• Published: Oxford University Press 19.06.2023
• ISSN: 1672-9145; 1745-7270
• DOI: 10.3724/abbs.2023089

Obesity has been reported to promote disordered folliculogenesis, but the exact molecular mechanisms are still not fully understood. In this study, we find that miR-133a is involved in obesity-induced follicular development disorder. After feeding with a high-fat diet (HFD) and fructose water for nine weeks, the mouse body weight is significantly increased, accompanied by an inflammatory state and increased expression of miR-133a in the adipose tissues and ovaries as well as accelerated follicle depletion. Although miR-133a is increased in the fat and ovaries of HFD mice, the increased miR-133a in the HFD ovaries is not derived from exosome transferred from obese adipose tissues but is synthesized by ovarian follicular cells in response to HFD-induced inflammation. In vivo experiments show that intrabursal injection of miR-133a agomir induces a decrease in primordial follicles and an increase in antral follicles and atretic follicles, which is similar to HFD-induced abnormal folliculogenesis. Overexpression of miR-133a modestly promotes granulosa cell apoptosis by balancing the expression of anti-apoptotic proteins such as C1QL1 and XIAP and pro-apoptotic proteins such as PTEN. Overall, this study reveals the function of miR-133a in obesity-induced ovarian folliculogenesis dysfunction and sheds light on the etiology of female reproductive disorders.