Abstract: Human embryo implantation is a highly dynamic and transient process orchestrated by sophisticated interplays between embryo and endometrium. Studying this crucial phase in-vitro has been limited by technical and ethical challenges. Here, we develop a 3D co-culture model by implanting blastoids into endometrial assembloids, which faithfully simulates human in-utero development and enables detailed exploration of maternal-fetal dynamics. Our system unveils implantation-triggered subpopulations, such as pioneering trophoblasts from blastoid derivatives fused with endometrial characteristics, and highly specialized ciliated epithelia within the endometrium that shed epithelial properties. The emergence of these subpopulations and the intense maternal-fetal crosstalk demonstrate active adaptations, responding coordinately to successful embryo implantation from both fetal and maternal perspectives. Additionally, our system highlights the critical roles of LIFR and CSF3 signalings in modulating embryo invasion. Overall, our study offers fresh insights into the mechanisms of embryo development and provides potential targets for reproductive research.
Funding Source: This work was supported by the National Natural Science Foundation of China (NSFC) (Grant Nos.32270850 and 32470843 to Y.W., Grant Nos. 92168205 to S.G., Grant Nos. 32370842 and 32100633 to Y.B.)
