1. Academic Validation
  2. Genetic landscape of human oocyte/embryo defects

Genetic landscape of human oocyte/embryo defects

  • Cell Genom. 2025 Sep 25:101012. doi: 10.1016/j.xgen.2025.101012.
Biaobang Chen 1 Weijie Wang 2 Juanzi Shi 3 Xiaoxi Sun 4 Yichun Guan 5 Guimin Hao 6 Junli Zhao 7 Jian Mu 8 Zhihua Zhang 8 Fangzhou Xu 8 Dengying Gao 8 Zhiqi Pan 8 Ran Yu 8 Hao Gu 8 Huizhen Fan 8 Yuxi Luo 8 Siyuan Xie 8 Xingzhu Du 8 Huixia Jing 8 Zhiqi Ye 8 Xuelin Zhang 8 Ruiqi Hai 8 Hongying Zhu 8 Tianyu Wu 8 Qiaoli Li 8 Jing Fu 4 Ling Wu 9 Wenjing Wang 10 Chunyi Li 11 Feiyang Diao 12 Qiuwen Shi 13 Lin Li 14 Shiru Xu 15 Da Li 16 Xi Dong 10 Peng Xu 17 Jiucun Wang 18 Lin He 19 Yanping Kuang 20 Qing Sang 21 Lei Wang 22
Affiliations

Affiliations

  • 1 Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China; NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.
  • 2 The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 3 Reproductive Medicine Center, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China.
  • 4 Shanghai Ji Ai Genetics and In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
  • 5 Center for Reproductive Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 6 Hebei Clinical Research Center for Birth Defects, Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • 7 Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
  • 8 Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.
  • 9 Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 10 Reproductive Medicine Center, Zhongshan Hospital of Fudan University, Shanghai, China.
  • 11 Shenyang Jinghua Hospital, Shenyang, Liaoning, China.
  • 12 Reproductive Medicine Center, Jiangsu Province Hospital, Nanjing, Jiangsu, China.
  • 13 Reproductive Medicine Center, The Third Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.
  • 14 Key Laboratory of Human Reproduction and Genetics, Department of Reproductive Medicine, Nanchang Reproductive Hospital, Nanchang, Jiangxi, China.
  • 15 Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong, China.
  • 16 Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
  • 17 Hainan Jinghua Hejing Hospital for Reproductive Medicine, Haikou, Hainan, China.
  • 18 State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China.
  • 19 Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
  • 20 Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: kuangyanp@126.com.
  • 21 Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China. Electronic address: sangqing@fudan.edu.cn.
  • 22 Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China; Shanghai Academy of Natural Sciences (SANS), Fudan University, Shanghai, China. Electronic address: wangleiwanglei@fudan.edu.cn.
Abstract

Oocyte/embryo defects can result in oocyte maturation arrest, fertilization failure, embryonic arrest, and infertility as well as recurrent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) failures. However, the genetic determinants of human oocyte/embryo defects remain largely unknown, and the overall genetic diagnostic yield for such defects has not been evaluated. Here, we performed exome Sequencing in 3,627 patients with oocyte/embryo defects. We identified a total of 479 positive cases carrying variants in 37 known genes, indicating a diagnostic yield of 13.2%. Case-control association studies combined with gene set enrichment analysis identified 123 novel candidate genes responsible for oocyte/embryo defects. These results provide a comprehensive genetic landscape of human oocyte/embryo defects and highlight the clinical significance of genetic counseling in infertile patients with oocyte/embryo defects. Our study will lay the foundation for transforming the traditional clinical practice for failed IVF/ICSI attempts into genetic-based precision and personalized treatment for these patients.

Keywords

exome sequencing; female infertility; genetic mutations; oocyte/embryo defects.

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