Abstract
Embryo development undergoes critical morphological transformations post-implantation, largely driven by the complex and dynamic microenvironment of the uterus. Despite advances, current 3D culture models inadequately recapitulate the uterine environment necessary for studying embryo-uterus interactions. In this work, we engineer a hydrogel inspired by the properties of the decidua, incorporating Matrigel to support blastocyst implantation and embryo development in vitro. Our findings reveal that embryos cultured within this hydrogel system successfully progress to an early organogenesis-like stage, including the development of first and second heart fields, mimicking natural embryogenesis. Moreover, we identify that the mechanical properties, particularly stress relaxation, play a crucial role in facilitating focal adhesion (FA) formation between the trophoblast and the hydrogel. Additionally, the degradation of the hydrogel by embryo-secreted metalloproteinases (MMP2 and MMP9) creates a favorable environment for continued embryonic growth and development. These insights contribute to a deeper understanding of how the external environment regulates embryo development and offer an enhanced approach for in vitro embryo culture.
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Data availability
The scRNA-Sequence data generated in this study have been deposited in the Chinese Academy of Sciences database under accession code PRJCA004049 [http://gsa.big.ac.cn/]. The SmartSeq2 data generated in this study have been deposited in the Chinese Academy of Sciences database under accession code PRJCA052100 [http://gsa.big.ac.cn/]. Source data are provided with this paper.
Code availability
The data analysis customized scripts are available to download from GitHub (https://github.com/dongjingxi/embryo-development-in-vitro.git).
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Acknowledgements
Q.G.’s work is supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0820000), National Natural Science Foundation of China (T2222029 and U21A20396), the Joint project of Chongqing Health Commission and Science and Technology Bureau (2025DBXM001), CAS Project for Young Scientists in Basic Research (YSBR-012), Beijing Institute for Stem Cell and Regenerative Medicine Project Incubation Fund (2022FH107), CAS Pioneer Hundred Talents Program (Y829F11102), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020802), and K. C. Wong Education Foundation (GJTD-2019-06). J.G.’s work is supported by the National Natural Science Foundation of China (32400684). Z.L.G.’s work is supported by the National Natural Science Foundation of China (32501207), and China Postdoctoral Science Foundation (2025M772889). S.J.’s work is supported by Natural Science Foundation of Beijing Municipality (7254546). We are grateful to Shiwen Li and Xili Zhu of the imaging platform of CAS for their outstanding support, and Chunli Li for help with a scanning electron microscope.
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Q.G., Q.Z., G.H.F., L.Q.Y., J.L.Z., and J.G. designed the experiments. J.G., J.W.L., Z.L.G., L.Y.W., and T.J. performed the experiments and analyzed the results. J.G. wrote the manuscript. J.X.D., Z.G., W.L., H.M.W., and S.J. provided assistance in carrying out experiments and discussed results. Q.G. supervised the work and revised the manuscript. J.G., J.W.L., Z.L.G., L.Y.W., and T.J. together with J.L.Z. and Q.G. discussed results and prepared the manuscript.
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Guo, J., Lyu, J., Gao, Z. et al. 3D biomimetic niche modulates embryo development in vitro. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68039-y
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DOI: https://doi.org/10.1038/s41467-025-68039-y
