Human embryo implantation begins with a brief and highly regulated interaction between the blastocyst and the endometrial surface. Because this process occurs inside the uterus during the earliest stages of pregnancy, observing it directly in humans remains extremely difficult.
In a study published in Science Advances, our team developed ADOC, an Adhesion Dynamics-On-A-Chip model designed to reproduce and study key features of human embryo adhesion to the endometrium.
Recreating a receptive human endometrium
ADOC combines organoid-derived endometrial epithelial cells and primary stromal cells in two microfluidic channels separated by a porous membrane. This configuration allows molecular communication between both cellular compartments and reproduces key structural and functional characteristics of the human endometrium.
Following hormonal preparation, the model showed features associated with the receptive phase of the menstrual cycle, including epithelial polarization, stromal decidualization, and communication between the epithelial and stromal compartments.
Single-cell transcriptomic analysis showed that hormonal treatment induced molecular profiles consistent with a receptive, mid-secretory endometrium.
Observing embryo adhesion in real time
After initially validating the model with mouse embryos, the researchers introduced human blastocysts donated for research.
Live imaging made it possible to observe how the embryos established stable contact with the endometrial epithelium, changed their morphology, and spread across its surface through the polar trophectoderm.
Nine of the nineteen human blastocysts studied under hormonally prepared conditions formed stable attachments. Beta-hCG secretion was also detected in the attached embryos analyzed for this function, supporting the maintenance of trophoblast activity during the experiment.
The results showed that adhesion depended on adequate hormonal preparation of the endometrium. None of the twelve embryos studied under hormone-free conditions established stable adhesion. Treatment with mifepristone, a progesterone receptor antagonist, also markedly reduced adhesion, with only one of eight embryos forming a stable attachment.
A platform for studying human implantation
ADOC does not reproduce the complete implantation process or the full complexity of the human endometrium. Its current design focuses on the earliest stages of embryo adhesion.
However, it provides a controlled human experimental system for studying embryo-endometrium interactions through live imaging and molecular analysis. The platform may also support research into altered endometrial receptivity, implantation disorders, and the effects of biological or pharmacological factors on embryo adhesion.
The study was co-first authored by Sofia Zaragozano and Maria Pardo-Figuerez and jointly supervised by Felipe Vilella and myself, with contributions from a multidisciplinary team of researchers and collaborators.
Article reference
Zaragozano S, Pardo-Figuerez M, Monteagudo-Sanchez A, et al. Modeling human embryo adhesion using a microfluidic platform. Science Advances. 2026;12(28):eadz2249. doi: 10.1126/sciadv.adz2249.