Implantation is a finely regulated process through which an embryo attaches to the endometrial epithelium and invades the uterine stroma. While previous studies have established endometrial organoids as 3-dimensional (3D) in vitro models of endometrial epithelial cells (EECs), they cannot fully recapitulate implantation because EECs of these organoids lack the typical apical-out polarity needed for blastocyst attachment. Here, Tamura and colleagues develop a novel mouse endometrial organoid where assemblies of epithelial and stromal cells self-organise to form a 3D ring-like structure, with EECs preferentially localising to the periphery and the stromal cells filling the inside without embedding in an extracellular matrix. The outer surfaces of the EECs exhibit structural and molecular characteristics of the apical side of the luminal epithelium, revealing that the new organoids possess an apical-out polarity that is necessary for implantation. Further, the authors find that the organoids, akin to the endometrium in vivo, respond to steroid hormones to become receptive to blastocyst attachment and can recapitulate the main steps of the early implantation process. Overall, this work reveals a new tractable 3D endometrial model that successfully incorporates both epithelial and stromal layers without the need for an extracellular matrix, and can be used to study embryo implantation.

© 2025. Published by The Company of Biologists Ltd
2025