2. Academic Validation
  3. 3D post-implantation co-culture of human embryo and endometrium

3D post-implantation co-culture of human embryo and endometrium

  • Cell Stem Cell. 2026 Jan 8;33(1):58-72.e7. doi: 10.1016/j.stem.2025.12.002.
Jinzhu Song 1,  Rusong Zhao 2,  Yu Zhang 3,  Minghui Lu 4,  Peishu Liu 5,  Tao Li 6,  Cheng Li 4,  Ruijie Yu 4,  Xueyao Chen 4,  Huajian Yang 4,  Xinwen Zhang 4,  Yining Su 4,  Yanli Han 4,  Duanchen Sun 7,  Qingbin Zhou 7,  Zhenzhen Hou 4,  Weijing Liu 4,  Xiaoyuan Gao 4,  Wenrong Tao 4,  Jingye Zhang 4,  Jingwen Wang 4,  Yingying Qin 8,  Hongmei Wang 9,  Keliang Wu 10,  Jun Wu 11,  Zi-Jiang Chen 12,  Han Zhao 13
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan 250012, Shandong, China.
  • 2 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Center for Clinical Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China; The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215000, Jiangsu, China.
  • 3 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
  • 4 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China.
  • 5 Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
  • 6 Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong First Medical University, Jinan 250022, Shandong, China.
  • 7 School of Mathematics, Shandong University, Jinan 250100, China.
  • 8 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong First Medical University, Jinan 250022, Shandong, China.
  • 9 Key State Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 10 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan 250012, Shandong, China. Electronic address: [email protected].
  • 11 Department of Molecular Biology, 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; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: [email protected].
  • 12 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan 250012, Shandong, China. Electronic address: [email protected].
  • 13 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan 250012, Shandong, China; Center for Clinical Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China. Electronic address: [email protected].
PMID: 41443195 DOI: 10.1016/j.stem.2025.12.002
Abstract

Embryo-maternal interaction is essential for post-implantation human development. While endometrial organoids have enabled in vitro modeling of the uterine environment, a fully integrated 3D co-culture system with human embryos has not been established. Here, we develop a physiologically relevant 3D platform that supports the co-culture of human embryos with endometrial organoids, enabling reciprocal embryo-maternal communication. This system sustains development to day 14 post-fertilization with structural and molecular fidelity to Carnegie stage landmarks, including yolk sac formation, primordial germ cell specification, and trophoblast maturation. Single-cell transcriptomics and functional assays reveal that the endometrial niche accelerates extravillous trophoblast emergence at day 9 post-fertilization and primes their invasive programs. Disruption of maternal signals, including human chorionic gonadotropin signaling blockade, markedly impairs embryonic progression. This co-culture system provides a powerful and tractable model to dissect human peri- and post-implantation development, with broad relevance to early pregnancy loss, placental biology, and reproductive medicine.

Keywords

Carnegie stage; embryo-endometrium interactions; endometrial organoids; extravillous trophoblast; fetal-maternal crosstalk; human blastocysts; human chorionic gonadotropin; human post-implantation development; primordial germ cell; syncytiotrophoblast.

Figures
Products