Advances and challenges of endometrial organoids in modeling endometrial function: basic, clinical, and future perspectives

As robust in vitro models that faithfully replicate the physiological functions of the human endometrium, endometrial organoids have emerged as pivotal tools for deciphering the regulatory mechanisms of endometrial receptivity and disease pathogenesis. Currently, insufficient vascularization and immunocompetence, phenotypic drift during long-term culture, and the absence of standardized protocols for clinical translation remain major challenges in endometrial organoid research. These limitations constrain their broader application in elucidating embryonic implantation mechanisms and advancing personalized therapeutics. In this review, we mainly introduce the recent progress in the endometrial organoids and their utility in studying endometrial development, decidualization regulation, and endometrial pathologies. Furthermore, we highlight the potential applications in reproductive medicine. Finally, we discussed the current challenges and future perspectives of endometrial organoid and its interdisciplinary integration. We anticipate that their translational potential will revolutionize the studies on uncovering the mechanisms of early implantation failure to inform diagnosis and therapeutics.