Human receptive endometrial assembloid 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 assembloids has provided a powerful model to examine this intricate biological process. In this study, we established a specialized human window-of-implantation (WOI) endometrial assembloid system that mimics the in vivo receptive endometrium. It recapitulates not only the structural attributes of pinopodes and cilia, but also molecular characteristics of mid secretory endometrium. Furthermore, the WOI endometrial assembloid exhibits hormone responsiveness, energy metabolism with larger and enhanced functional mitochondria, increased ciliary assembly and motility, and epithelial-mesenchymal transition (EMT), as well as promising potential for embryo implantation. As such, WOI assembloids hold great promise as a platform to unravel the intricate mechanisms governing endometrial receptivity regulation, maternal-fetal interactions, and associated diseases, ultimately driving impactful advancements in the field.