A 3D in vitro model for studying human implantation and implantation failure

  • Cell. 2026 Jan 8;189(1):70-86.e20. doi: 10.1016/j.cell.2025.10.026.
Qian Li  1 ,  Yang Yuan  2 ,  Wentao Zhao  3 ,  Yuanjun Li  1 ,  Juanzi Shi  4 ,  Yu Xiu  5 ,  Mi Han  6 ,  Yan Han  3 ,  Junmei Zhang  2 ,  Shuhan Cheng  3 ,  Xin Qi  5 ,  Xizhuang Sun  3 ,  Tan Jia  3 ,  Jiaqi Xing  7 ,  Siwei Deng  5 ,  Xiaodi Yan  3 ,  Seiya Oura  8 ,  Hongfei Li  8 ,  Ying Sun  9 ,  Huiyao Yuan  3 ,  Xiaohong Ma  4 ,  Miaomiao Xin  4 ,  Jianchao Zhao  3 ,  Xili Zhu  1 ,  Cong Wang  10 ,  Qin Wang  10 ,  Ge Lin  6 ,  Xiaokui Yang  11 ,  Yulei Wei  12 ,  Jun Wu  13 ,  Hongmei Wang  14 ,  Leqian Yu  15
Affiliations
  • 1. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • 2. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4. The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an 710003, Shaanxi, China.
  • 5. State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
  • 6. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410000, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410000, China.
  • 7. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 8. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 9. School of Food and Health, Beijing Technology and Business University, Beijing 100048, China.
  • 10. Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China.
  • 11. Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China. Electronic address: [email protected].
  • 12. State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: [email protected].
  • 13. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: [email protected].
  • 14. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
  • 15. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID: 41443192 DOI: 10.1016/j.cell.2025.10.026
Abstract

A better understanding of human implantation is essential for improving assisted reproduction outcomes and addressing recurrent implantation failure (RIF). However, ethical constraints and limited access to human embryos make direct studies challenging. To overcome this, we developed a 3D in-chip implantation model using human blastoids or blastocysts co-cultured with a bioengineered human endometrial tissue, termed endometrioid. This system successfully recapitulates key events of human implantation and early post-implantation development. Importantly, when modeling implantation using samples derived from RIF patients, we observed significantly reduced blastoid implantation capability compared with endometrioids from fertile controls. Furthermore, a targeted screen of U.S. Food and Drug Administration (FDA)-approved compounds identified candidates that markedly enhanced implantation efficiency in RIF-derived endometrioids. Together, this 3D platform enables mechanistic investigation of human implantation and implantation failure and offers a scalable approach to evaluate therapeutic strategies for improving embryo-endometrium interaction in a clinical setting.

Keywords
endometrioid; human blastoid; human early development; human implantation; recurrent implantation failure; stem cell-derived embryo model.
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