Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage

作     者：Zhu, Shiqi Xie, Peng Yang, Yi Wang, Yan Zhang, Chuanxin Zhang, Yu Si, Shuhan Zhang, Jin He, Jingjing Si, Hao Fang, Ke Ma, Binbin Jiang, Xu Huang, Lindi Li, Jiamin Min, Tian Zheng, Beihong Da, Lincui Lin, Dianliang Gao, Kun Li, Yuanyuan Huang, Mingtao Qiao, Fengchang Huo, Haiqin Feng, Haoyang Zhao, Han Chen, Zijiang Xu, Zhengfeng Xie, Jing Cao, Hua Liu, Jin Yao, Xuebiao Xie, Wei Sun, Yan Wu, Keliang Xiong, Bo Hu, Ping Luo, Zhuojuan Lin, Chengqi 

作者机构：Southeast Univ Sch Life Sci & Technol Key Lab Dev Genes & Human Dis Nanjing Peoples R China Nantong Univ Coinnovat Ctr Neuroregenerat Nantong Peoples R China Southeast Univ Sch Biol Sci & Med Engn Nanjing Peoples R China Nanjing Med Univ Womens Hosp Dept Prenatal Diag Nanjing Peoples R China Shandong Univ Ctr Reprod Med Jinan Peoples R China Zhejiang Univ Coll Anim Sci Hangzhou Peoples R China Tongji Univ Sch Life Sci & Technol Shanghai Peoples R China Fujian Matern & Child Hlth Hosp Reprod Med Ctr Fujuan 350001 Peoples R China Chinese Univ Hong Kong Sch Data Sci Shenzhen Peoples R China Univ Sci & Technol China Sch Life Sci Lab Organelle Dynam & Plast Control Hefei 230026 Peoples R China Southeast Univ Shenzhen Res Inst Shenzhen Peoples R China Southeast Univ Sch Life Sci & Technol Jiangsu Prov Key Lab Crit Care Med Nanjing Peoples R China 

出 版 物：《NATURE STRUCTURAL & MOLECULAR BIOLOGY》 (Nat. Struct. Mol. Biol.)

年 卷 期：2025年第32卷第2期

页      面：1-12页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：National Natural Science Foundation of China [32350004, 32030017, 32470627] National Key R&D Program of China [2018YFA0800100] Shenzhen Science and Technology Program [JCYJ20220530160417038, JCYJ20220530160416037] 

摘      要：Up to an estimated 10% of women experience miscarriage in their lifetimes. Embryonic aneuploidy is a leading cause for miscarriage, infertility and congenital defects. Here we identify variants of ELL3, a gene encoding a transcription elongation factor, in couples who experienced consecutive early miscarriages due to embryonic aneuploidy. Maternal ELL3 knockout leads to mouse oocyte aneuploidy, subfertility and miscellaneous embryonic defects. Mechanistically, we find that ELL3 localizes to the spindle during meiosis, and that ELL3 depletion in both mouse and human oocytes increases the incidence of meiotic spindle abnormality. ELL3 coordinates with TPX2 to ensure the proper function of the microtubule motor KIF11. Live imaging analysis shows that ELL3 is paramount for promoting spindle assembly and driving chromosome movement. Together, our findings implicate maternal ELL3 deficiency in causing oocyte aneuploidy and early miscarriage.