2. Academic Validation
  3. Comparative proteomic landscapes elucidate human preimplantation development and failure

Comparative proteomic landscapes elucidate human preimplantation development and failure

  • Cell. 2025 Feb 6;188(3):814-831.e21. doi: 10.1016/j.cell.2024.12.028.
Wencheng Zhu 1,  Juan Meng 2,  Yan Li 3,  Lei Gu 4,  Wenjun Liu 2,  Ziyi Li 5,  Yi Shen 5,  Xiaoyu Shen 2,  Zihong Wang 2,  Yonggen Wu 3,  Guiquan Wang 6,  Junfeng Zhang 5,  Huiping Zhang 5,  Haiyan Yang 3,  Xi Dong 7,  Hui Wang 4,  Xuefeng Huang 3,  Yidi Sun 8,  Chen Li 9,  Liangshan Mu 10,  Zhen Liu 11
Affiliations

Affiliations

  • 1 Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China. Electronic address: wczhu@ion.ac.cn.
  • 2 Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 4 State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 5 Shanghai Applied Protein Technology Co., Ltd., Shanghai 201100, China.
  • 6 Center for Reproductive Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen 361102, China.
  • 7 Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 8 Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China; State Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai, China. Electronic address: ydsun@ion.ac.cn.
  • 9 State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: cli@shsmu.edu.cn.
  • 10 Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: mu.liangshan@zs-hospital.sh.cn.
  • 11 Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China. Electronic address: zliu2010@ion.ac.cn.
PMID: 39855199 DOI: 10.1016/j.cell.2024.12.028
Abstract

Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species. Integrative analysis with translatomic data revealed extensive divergence between translation activation and protein accumulation. Multi-omic analysis indicated that ZGA transcripts often contribute to protein accumulation in blastocysts. Using mouse embryos, we identified several transcriptional regulators critical for early development, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics of poor-quality embryos from over 100 patient couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening avenues for addressing human infertility.

Keywords

ZGA; human preimplantation development; multi-omic analysis; poor-quality embryo; ultrasensitive proteomics.

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