Combining Endometrial Assembloids and Blastoids to Delineate the Molecular Roadmap of Implantation

Implantation is the process by which a competent blastocyst burrows into the receptive uterus to support embryo development. Successful implantation is of the utmost importance to pregnancy. However, due to the short window and difficulty in accessing the uterus in vivo during implantation, including ethical considerations, our understanding of the molecular network that safeguards this process remains incomplete. The use of three-dimensional (3D) culture systems has significant advantages as it recapitulates many aspects of the tissue organization and cell composition seen in vivo. With the recent advent of endometrial organoids and blastoids, it is now feasible to establish an in vitro implantation culture model to dissect the molecular signaling networks that are critical for implantation. In this review, we briefly summarize the current methodology for generating endometrial organoids and blastoids, along with the applications of these organoids for research on implantation. Incorporating stromal and immune cells, blood vessels, and others into the current endometrial organoid could build a more complete model of the endometrium, which can be combined with blastoids to model blastocyst implantation in vitro. We envision that this novel 3D system can be employed to elucidate the molecular mechanisms required for successful implantation.