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

作　　者：Ruizhi Chen Xueqing Wu Han Qiu Baiming Yang Yao Chen Xiang Chen Yingshan Li Shaochun Yuan Dan Liu Luanjuan Xiao Yanhong Yu 

机构地区：[1]Key Laboratory of Regenerative Medicine(JNU-CUHK),Ministry of Education,Department of Developmental and Regenerative Biology,College of Life Science and Technology,Jinan University,Guangzhou 510632,China [2]Guangdong Province Key Laboratory of Pharmaceutical Functional Genes,College of Life Sciences,Sun Yat-Sen University,Guangzhou 510275,China [3]Department of Women’s HealthCare,Affiliated Foshan Women and Children’s Hospital,Southern Medical University,Foshan 528000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第8期1234-1246,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Science and Technology Program of Guangzhou,China(No.201904010041);the Guangdong Basic and Applied Basic Research Foundation(No.2020A1515010033);the National Natural Science Foundation of China(No.30900232);the Guangdong Science and Technology Department Foundation(No.2020B1212060031);the Research Grant of Key Laboratory of Regenerative Medicine,Ministry of Education,Jinan University(No.ZSYXM202207).

摘　　要：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 obesityinduced ovarian folliculogenesis dysfunction and sheds light on the etiology of female reproductive disorders.

关 键 词：abnormal follicular development INFLAMMATION miR-133a OBESITY 

分 类 号：R575[医药卫生—消化系统]