An endometrium-on-a-chip model captures the first moments of human embryo adhesion

Understanding how a human embryo first attaches to the endometrium has long been one of the biggest challenges in implantation research. These events take place during the earliest stages of pregnancy and cannot be observed directly in humans.

Researchers at the Carlos Simon Foundation have now developed ADOC (Adhesion Dynamics-On-A-Chip), a microfluidic model of the human endometrium that recreates key features of the receptive uterine environment and allows these early interactions to be studied under controlled conditions. The work has been published in Science Advances.

A human endometrium on a chip

ADOC combines organoid-derived endometrial epithelial cells with primary stromal cells cultured in two interconnected microfluidic channels. Together, these cells reproduce several structural and functional characteristics of the human endometrium.

After hormonal preparation, the model developed features associated with endometrial receptivity, including epithelial polarization, stromal decidualization and communication between both cell compartments. Single-cell transcriptomic analyses confirmed that the tissue acquired molecular features consistent with the receptive phase of the menstrual cycle.

Watching embryo adhesion as it happens

After validating the platform with mouse embryos, the researchers introduced human blastocysts donated for research.

Using live imaging, they observed how embryos established their first stable contact with the epithelial surface, gradually spread through the polar trophectoderm and initiated the earliest stages of adhesion.

Nine of the nineteen embryos formed stable attachments. These embryos also secreted beta-hCG, indicating that trophoblast function was maintained throughout the experiment.

The study further showed that stable adhesion depended on hormonal preparation of the endometrium. Embryos failed to attach when the tissue was not hormonally primed, and treatment with the progesterone receptor antagonist mifepristone significantly reduced adhesion.

A new tool for implantation research

Although ADOC does not reproduce every stage of implantation, it provides a human experimental platform for investigating one of its earliest and least accessible events.

The model offers new opportunities to study embryo-endometrium interactions, investigate altered endometrial receptivity and evaluate factors that may influence implantation in a controlled human setting.

The study was co-first authored by Sofia Zaragozano and Maria Pardo-Figuerez, and led by Felipe Vilella and Carlos Simon, together with a multidisciplinary team of researchers and collaborators.