Researchers at the Babraham Institute and Stanford University have developed a laboratory model that closely mimics the human womb lining, enabling new research into how embryos implant. This development is expected to help scientists better understand why implantation sometimes fails, which is a major cause of early pregnancy loss and complications.
"Understanding embryo implantation and embryo development just after implantation has significant clinical relevance as these stages are particularly prone to failure," said Dr Peter Rugg-Gunn, senior group leader at the Babraham Institute who led the study. "In particular, the high rate of implantation failure represents one of the main limiting factors for IVF success."
The process of embryo embedding into the womb lining occurs about a week after fertilization but has been difficult to observe directly until now. The researchers built their model by combining two main cell types found in endometrial tissue—epithelial cells and stromal cells—sourced from healthy donors who provided endometrial biopsies. These were grown together in a gel designed to mimic the natural structure of the womb lining.
When tested with donated early-stage human embryos from IVF procedures, this engineered tissue showed similar responses to real endometrial tissue during embryo adhesion and invasion. After implantation in this model, embryos increased secretion of hormones like human chorionic gonadotropin (hCG), which is used in pregnancy tests, as well as other proteins associated with pregnancy.
Dr Rugg-Gunn noted: "We were really excited to see that our system released essential factors that are needed to nourish the embryo in the first few weeks of pregnancy. Previous models haven't been able to achieve this, so this represented a breakthrough for us."
The model also supported further embryonic development up to 12-14 days post-fertilization—a stage rarely studied before—and allowed researchers to observe important milestones such as specialized cell formation and precursor cells necessary for placenta development.
Using single-cell analysis at points where embryos implanted into the artificial lining, scientists were able to study how cells communicate during early pregnancy. This work provides new information about interactions between embryos and their environment immediately after implantation.
Dr Irene Zorzan, co-first author of the study and postdoctoral fellow, explained: "Embryo implantation and post-implantation development are crucial events normally hidden from view, and this has limited our ability to explore the cellular and molecular mechanisms underlying this critical phase.
"Now, we can witness the unexplored aspects of the earliest moments of development and uncover new insight into how the foundations of a successful pregnancy are laid".
The research team suggests that their model could eventually be used both for studying infertility—by comparing responses between different individuals—and for testing potential treatments aimed at improving embryo reception by the womb lining.
Dr Sarah Elderkin, co-first author of the study and senior research scientist, concluded: "The synchronised communications between the embryo and womb lining are essential for a healthy baby and a healthy mother. Our model provides the ability for us to understand how this connection is established at implantation with implications for infertility, improving pregnancy success and early identification of pregnancy disorders. We are hugely grateful to people who donate surplus embryos to enable research like ours, without whom it wouldn't be possible."
