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

Qian Li¹, Yang Yuan², Wentao Zhao³, Yuanjun Li¹, Juanzi Shi⁴, Yu Xiu⁵, Mi Han⁶, Yan Han³, Junmei Zhang², Shuhan Cheng³, Xin Qi⁵, Xizhuang Sun³, Tan Jia³, Jiaqi Xing⁷, Siwei Deng⁵, Xiaodi Yan³, Seiya Oura⁸, Hongfei Li⁸, Ying Sun⁹, Huiyao Yuan³, Xiaohong Ma⁴, Miaomiao Xin⁴, Jianchao Zhao³, Xili Zhu¹, Cong Wang¹⁰, Qin Wang¹⁰, Ge Lin⁶, Xiaokui Yang¹¹, Yulei Wei¹², Jun Wu¹³, Hongmei Wang¹⁴, Leqian Yu¹⁵

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: yangxiaokui@ccmu.edu.cn.
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: yulei.wei@cau.edu.cn.
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: jun2.wu@utsouthwestern.edu.
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: wanghm@ioz.ac.cn.
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: leqianyu@ioz.ac.cn.

PMID: 41443192
DOI: 10.1016/j.cell.2025.10.026

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

Qian Li et al. Cell. 2026.

. 2026 Jan 8;189(1):70-86.e20.

doi: 10.1016/j.cell.2025.10.026. Epub 2025 Dec 23.

Authors

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: yangxiaokui@ccmu.edu.cn.
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: yulei.wei@cau.edu.cn.
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: jun2.wu@utsouthwestern.edu.
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: wanghm@ioz.ac.cn.
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: leqianyu@ioz.ac.cn.

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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Conflict of interest statement

Declaration of interests L.Y., H.W., Q.L., Y.W., and Y.X. have filed a patent application based on this work.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Other Literature Sources