Human receptive endometrial organoid for deciphering the implantation window

Abstract Human endometrial receptivity is a critical determinant of pregnancy success; however, in vivo studies of its features and regulation are particularly challenging due to ethical restriction. Recently, the development of human endometrial organoids has provided a powerful model to examine this intricate biological process. In this study, we established a specialized human window-of-implantation (WOI) endometrial organoid system that mimics the in vivo receptive endometrium. The endometrial organoid recapitulates not only the structural attributes of glands and stroma, but also the in vivo endometrium’s cell types at the single-cell level. Furthermore, the WOI endometrial organoid exhibits the features of in vivo implantation endometrium such as hormone responsiveness, secretory functions, and distinctive implantation window hallmarks, including decidualization, extracellular matrix (ECM) remodeling, pinopode formation, cilia generation and metabolism. This in vitro model also effectively demonstrates the process of proliferation-secretory transformation, ciliary epithelium differentiation, and epithelial-mesenchymal transition (EMT). As such, WOI organoids hold great promise as a robust platform to unravel the intricate mechanisms governing endometrial receptivity regulation, maternal-fetal interactions, and associated diseases, ultimately driving impactful advancements in the field.