Epg5 deficiency leads to primary ovarian insufficiency due to WT1 accumulation in mouse granulosa cells
Year: 2022
Type: dataset
Abstract: Primary ovarian insufficiency (POI), also known as premature ovarian failure, is an ovarian defect in humans characterized by the premature depletion of ovarian follicles before the age of 40. However, the mechanisms underlying POI remain largely unknown. Here, we show that knockout of Epg5 (ectopic P-granules autophagy protein 5 homolog (C. elegans)) results in subfertility in female mice, which exhibit a POI-like phenotype. Single-cell RNA sequencing analysis revealed that the knockout of Epg5 affected the differentiation of granulosa cells (GCs). Further investigation demonstrated that knockout of Epg5 blocks macroautophagic/autophagic flux, resulting in the accumulation of WT1 (WT1 transcription factor), an essential transcription factor for GCs, suggesting WT1 needs to be selectively degraded by the autophagy pathway. We found that the insufficient degradation of WT1 in the antral follicular stage contributes to reduced expression of steroidogenesis-related genes, thereby disrupting GC differentiation. Collectively, our studies show that EPG5 promotes WT1 degradation in GCs, indicating that the dysregulation of Epg5 in GCs can trigger POI pathogenesis. Abbreviations: 3-MA, 3-methyladenine; CHX, cycloheximide; CQ, chloroquine; EPG5, ectopic P-granules autophagy protein 5 homolog (C. elegans); GC, granulosa cell; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MII, metaphase II; POI, primary ovarian insufficiency; PB1, polar body 1; SQSTM1/p62, sequestosome 1; WT1, WT1 transcription factor
Source: Figshare
Authors: Liu, Wenwen, Chen, Min, Liu, Chao, Wang, Liying, Wei, Huafang, Zhang, Ruidan, Ren, Zhengxing, Chen, Yinghong, Luo, Mengcheng, Zhao, Jianguo, Jiang, Hongwei, Gao, Fei, Li, Wei
Institutions: Weifang Medical University, Chinese Academy of Agricultural Sciences, Qingdao Institute of Bioenergy and Bioprocess Technology, Nanjing Agricultural University, Fujian Medical University, Guangdong Medical College, South China Normal University, Xiamen University, Jilin University, Shandong Normal University, Wuhan University, Third Affiliated Hospital of Guangzhou Medical University, Second Affiliated Hospital of Chongqing Medical University, Guangdong Academy of Agricultural Sciences, Northwest Institute of Eco-Environment and Resources, Nanjing Drum Tower Hospital, The First Hospital of Kunming, Yunnan Center for Disease Control And Prevention, Peking University First Hospital, Science and Technology Commission of Shanghai Municipality, Institute of Botany, Northeast Forestry University, Hunan Agricultural University, Southern Medical University, East China Normal University, Southeast University, Nanjing Medical University, Hunan Institute of Technology, Dalian Ocean University, Hebei Medical University, Central South University, Harbin Medical University, Zunyi Medical University, Shanghai Jiao Tong University, Guangdong University of Foreign Studies, Chinese Academy of Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Forestry University, University of Jinan, Guangzhou Women and Children Medical Center, Shandong Academy of Agricultural Sciences, Affiliated Hospital of Qingdao University, Institute of Optics and Electronics, Chinese Academy of Sciences, Peking University Third Hospital, First Affiliated Hospital of Bengbu Medical College, Jiangsu Province Hospital, First Affiliated Hospital of Soochow University, First Affiliated Hospital of Jinan University, Shandong First Medical University, University of Chinese Academy of Sciences, Qingdao University of Technology, Huazhong University of Science and Technology, Zhejiang University, University of South China, First Hospital of Jilin University, Jinzhou Medical University, Shanxi Datong University, Minzu University of China, École des Hautes Études en Santé Publique, National University of Singapore, Chinese PLA General Hospital, Zhengzhou University, Institute of Genetics and Developmental Biology, Duke-NUS Medical School, First Affiliated Hospital of Chengdu Medical College, Shanghai Sixth People's Hospital, National Heart Centre Singapore, Chengdu University of Traditional Chinese Medicine, Air Force Medical University, Tongji University, Inner Mongolia Agricultural University, University of Science and Technology of China, Ministry of Education of the People's Republic of China, University of Electronic Science and Technology of China, Army Medical University, Shandong University, Nanjing Forestry University, Northeast Agricultural University, Baylor College of Medicine, Capital Medical University, Nanjing University of Information Science and Technology, Peking University, University of California, Irvine, China-Japan Friendship Hospital, Soochow University, Institute of Hydrobiology, West China Hospital of Sichuan University, Heilongjiang Provincial Academy of Agricultural Sciences, International Peace Maternity & Child Health Hospital, The People's Hospital of Guangxi Zhuang Autonomous Region, Second Affiliated Hospital of Soochow University, The First Affiliated Hospital, Sun Yat-sen University, Institute of Hydrobiology, Biology Centre, Academy of Sciences of the Czech Republic, National Institute for Communicable Disease Control and Prevention, Children's Hospital of Suzhou University, First Affiliated Hospital of Zhengzhou University, First Affiliated Hospital of Hebei Medical University, Xiangya Hospital Central South University, Chinese People's Liberation Army, Children's Hospital of Capital Institute of Pediatrics, Indiana University – Purdue University Indianapolis, Northwest Normal University, Shandong Agricultural University, Xi'an Jiaotong University, Tsinghua University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4394357089