A human endometrium-on-chip platform for functional assessment of luminal epithelial receptivity.

Successful embryo implantation requires timely acquisition of endometrial receptivity, yet the epithelial mechanisms governing this transition remain poorly understood and difficult to study in humans. Current clinical assessments rely largely on transcriptomic markers, despite limited evidence that these predict functional implantation outcomes. Here, we present a human endometrium-on-chip model that enables controlled hormonal priming and quantitative measurement of blastoid attachment to patient-derived luminal epithelium. We show that hormonally primed epithelial monolayers maintain attachment competence across extended progesterone exposure, indicating a sustained permissive state rather than a sharply defined window of implantation. Single-cell RNA sequencing reveals a continuous maturation trajectory that is decoupled from functional adhesion. The model further recapitulates localized epithelial remodeling at blastoid contact sites. Together, this system provides a mechanistic framework to interrogate epithelial determinants of implantation, challenges marker-based definitions of receptivity, and offers a foundation for future diagnostic and personalized applications in medically assisted reproduction.