3D post-implantation co-culture of human embryo and endometrium
Jinzhu Song, RuSong Zhao, Yu Zhang, Minghui Lu, Peishu Liu, tao li, Cheng Li, Ruijie Yu, Xueyao Chen, Huajian Yang, Xinwen Zhang, Yining Su, Yanli Han, Duanchen Sun, Qi Zhou, Zhenzhen Hou, Weijing Liu, Xiaoyuan Gao, Wenrong Tao, JingYe Zhang, J. Wang, Yingying Qin, Hongmei Wang Hongmei Wang, Keyi Wu, Jun Wu, Zi‐Jiang Chen, Han Zhao
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.