Reconstructing the Human Endometrium In Vitro: Current Three-Dimensional (3D) Models and Future Perspectives

There are differences between artificial 3D systems and ex vivo model systems, but they are same in trying to mimic the similarity to in vivo tissue or organs, here we put them in a 3D model. This review summarizes current 3D endometrial models, including extracellular matrix (ECM) and hydrogel-based systems, endometrial organoids and assembloids, and advanced engineered platforms such as microfluidic organ-on-a-chip systems and 3D bioprinting, as well as advanced ex vivo organotypic, native-preserved 3D systems. These models have enabled the investigation of endometrial functions, including hormone-dependent epithelial differentiation, stromal decidualization, epithelial-stromal crosstalk, and trophoblast invasion, as well as embryo-endometrium interactions. Despite these advances, individual models reproduce only selected biochemical, cellular, spatial, or dynamic features of the native endometrium, and challenges remain in achieving physiological relevance together with reproducibility, standardization, and experimental accessibility. This review further argues that future 3D endometrial models should balance physiological relevance with reproducibility, standardization, and experimental accessibility, rather than simply increasing model complexity. Such models may provide improved platforms for studying uterine endometrial physiology, implantation, and reproductive disorders.