Modeling human embryo adhesion using a microfluidic platform

Abstract Embryo adhesion represents the first step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We tested its function by introducing mouse and human blastocysts and showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage segregation. Moreover, human embryos secreted βhCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity, and disorders affecting embryo-endometrium interactions. Teaser Endometrium-on-a-chip shows detailed human embryo adhesion dynamics.