Genetic landscape of human oocyte/embryo defects
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.
Authors
- Xingzhu Du
- Fangzhou Xu (ORCID: https://orcid.org/0000-0001-7660-1206)
- Z. Ye
- Yichun Guan (ORCID: https://orcid.org/0000-0002-6255-2551)
- Ling Wu (ORCID: https://orcid.org/0000-0001-9217-9412)
- Hao Gu (ORCID: https://orcid.org/0000-0002-4824-1992)
- Xuelin Zhang (ORCID: https://orcid.org/0000-0002-7477-344X)
- Peng Hui Xu (ORCID: https://orcid.org/0000-0002-9593-7167)
- Feiyang Diao (ORCID: https://orcid.org/0000-0003-0118-3382)
- Dengying Gao (ORCID: https://orcid.org/0000-0003-1895-0373)
- Junli Zhao (ORCID: https://orcid.org/0000-0003-3527-0978)
- Xiaoxi Sun (ORCID: https://orcid.org/0000-0002-3366-5821)
- Juanzi Shi (ORCID: https://orcid.org/0000-0002-9040-7829)
- Jiucun Wang (ORCID: https://orcid.org/0000-0003-2765-0620)
- Biaobang Chen (ORCID: https://orcid.org/0000-0002-9921-2155)
- Yanping Kuang (ORCID: https://orcid.org/0000-0003-2985-5793)
- Guimin Hao (ORCID: https://orcid.org/0000-0002-0185-8442)
- Qing Sang (ORCID: https://orcid.org/0000-0002-9895-1394)
- Huizhen Fan
- Tianyu Wu (ORCID: https://orcid.org/0000-0002-4295-7172)
- Qiaoli Li (ORCID: https://orcid.org/0000-0002-8495-7103)
- Yuxi Luo (ORCID: https://orcid.org/0000-0001-6575-0783)
- Zhiqi Pan
- Hongmei Jing (ORCID: https://orcid.org/0000-0003-4958-2489)
- Da Li (ORCID: https://orcid.org/0000-0002-4895-1185)
- Zhihua Zhang (ORCID: https://orcid.org/0000-0002-4725-883X)
- Weijie Wang (ORCID: https://orcid.org/0000-0002-5717-1818)
- Lin Li (ORCID: https://orcid.org/0000-0002-6798-023X)
- Wenjing Wang (ORCID: https://orcid.org/0000-0002-4019-4589)
- Lei Wang (ORCID: https://orcid.org/0000-0002-3400-0434)
- Ran Yu (ORCID: https://orcid.org/0009-0008-1017-7332)
- Chunyi Li (ORCID: https://orcid.org/0000-0001-7275-4440)
- Xi Dong
- Jing Fu (ORCID: https://orcid.org/0000-0002-4804-821X)
- Qiuwen Shi
- Ruiqi Hai (ORCID: https://orcid.org/0009-0003-5237-8304)
- Siyuan Xie
- Lin He
- Shiru Xu
- Jian Mu
- Hongying Zhu
Institutions
- Hebei Medical University (CN)
- Guangxi Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- Shanghai Ninth People's Hospital (CN)
- Second Hospital of Hebei Medical University (CN)
- Northwest Women's and Children's Hospital (CN)
- Jiangxi Maternal and Child Health Hospital (CN)
- International Peace Maternity & Child Health Hospital (CN)
- Zhongshan Hospital (CN)
- Ningxia Medical University (CN)
- Hainan General Hospital (CN)
- Ningxia Medical University General Hospital (CN)
- Shenyang 242 Hospital (CN)
- Third Affiliated Hospital of Zhengzhou University (CN)
- Obstetrics and Gynecology Hospital of Fudan University (CN)
- Jiangsu Province Hospital (CN)
- Shenzhen Zhongshan Urological Hospital (CN)
- Children's Hospital of Fudan University (CN)
- China Medical University (CN)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1016/j.xgen.2025.101012
- Citations
- 3
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 5.64