Genetic landscape of human oocyte/embryo defects

Biaobang Chen¹, Weijie Wang², Juanzi Shi³, Xiaoxi Sun⁴, Yichun Guan⁵, Guimin Hao⁶, Junli Zhao⁷, Jian Mu⁸, Zhihua Zhang⁸, Fangzhou Xu⁸, Dengying Gao⁸, Zhiqi Pan⁸, Ran Yu⁸, Hao Gu⁸, Huizhen Fan⁸, Yuxi Luo⁸, Siyuan Xie⁸, Xingzhu Du⁸, Huixia Jing⁸, Zhiqi Ye⁸, Xuelin Zhang⁸, Ruiqi Hai⁸, Hongying Zhu⁸, Tianyu Wu⁸, Qiaoli Li⁸, Jing Fu⁴, Ling Wu⁹, Wenjing Wang¹⁰, Chunyi Li¹¹, Feiyang Diao¹², Qiuwen Shi¹³, Lin Li¹⁴, Shiru Xu¹⁵, Da Li¹⁶, Xi Dong¹⁰, Peng Xu¹⁷, Jiucun Wang¹⁸, Lin He¹⁹, Yanping Kuang²⁰, Qing Sang²¹, Lei Wang²²

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.

PMID: 41005306
DOI: 10.1016/j.xgen.2025.101012

Free article

Genetic landscape of human oocyte/embryo defects

Biaobang Chen et al. Cell Genom. 2025.

Free article

. 2025 Sep 25:101012.

doi: 10.1016/j.xgen.2025.101012. Online ahead of print.

Authors

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.

PMID: 41005306
DOI: 10.1016/j.xgen.2025.101012

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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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Genetic landscape of human oocyte/embryo defects

Affiliations

Genetic landscape of human oocyte/embryo defects

Authors

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources