Synopsis
Embryo implantation is a crucial step for the establishment of pregnancy and consists of three sequential stages: apposition, adhesion to the endometrium, and invasion into the decidua. Among these, embryo adhesion is a highly coordinated process that remains poorly understood due to the lack of physiologically relevant human in vitro models capable of capturing these early events. To address this challenge, researchers from the Carlos Simon Foundation have developed a human Endometrium-on-a-Chip using Emulate’s Organ-on-a-Chip technology to recreate the dynamic endometrial microenvironment.
The Endometrium-on-a-Chip was established by combining organoid-derived endometrial epithelial cells in the upper channel with primary endometrial stromal cells in the lower channel. The model was optimized to generate a stable and hormonally responsive endometrial tissue and characterized through the assessment of epithelial polarization, extracellular vesicle secretion, epithelial receptivity, and stromal decidualization.
Single-cell RNA sequencing was performed to define the cellular composition of the model and characterize the identity and heterogeneity of both epithelial and stromal populations. The platform was further used to investigate how pharmacological disruption of endometrial receptivity with mifepristone influences embryo attachment, with changes in receptivity-associated gene expression confirming the effect of the treatment.
The model was validated by introducing mouse embryos as a proof of concept, demonstrating its suitability for studying the initial stages of embryo implantation. Human blastocysts were then incorporated into the platform to capture and characterize the events associated with embryo adhesion, revealing trophectoderm-mediated attachment, embryo reorganization, and trophoblast functionality and differentiation.
Together, these findings establish the Endometrium-on-a-Chip as a robust and physiologically relevant platform for investigating early embryo implantation and endometrial receptivity. The versatility of the model also provides a foundation for future applications, including modeling endometrial disorders and evaluating pharmacological modulation in a human-relevant in vitro system.
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