17/12/2025
Key points:
By engineering a system replicating the womb lining with high biological accuracy, researchers at the Babraham Institute and Stanford University have been able to study the implantation of human embryos, opening up this enigmatic process to investigation. This now allows scientists to study interactions between the womb and embryo, and look for the causes behind implantation failure, a main reason for early pregnancy loss, and the origins of pregnancy 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.”
About one week after fertilisation, the developing embryo embeds into the womb lining (endometrium). This stage in development is one of the least understood due to the difficulty of observing the embryo during and after implantation.
Engineering the womb lining model
The new 3D model system looks to replicate the complex physiological properties and cellular composition of the endometrium. The model is built in a step-by-step process by bringing together the different components of endometrial tissue. The team isolated two essential cell types that form endometrial tissue – epithelial cells and stromal cells – from tissue donated by healthy people who had endometrial biopsies.
As well as the cell types, the researchers sought to recreate the structure of the womb lining. Information from donated endometrial tissue was used to identify the tissue components that give the womb lining its structure. The researchers were able to incorporate these components together with the stromal cells into a special type of gel to support the growth of the cells in a thick layer. On top of this, they added the epithelial cells, which spread out over the surface of the stromal cells.
Once assembled, this formed an advanced replica of the womb lining, matching a biopsy of endometrial tissue in terms of cellular architecture, and showing responses to hormone stimulation that indicate the engineered womb lining’s receptivity for embryo implantation.
Witnessing implantation and the hallmarks of post-implantation development
The team tested their model using donated early-stage human embryos from IVF procedures, and found that the embryo – at this point a compact ball of cells – underwent the expected stages expected of adhesion and invasion into the endometrial scaffold. Following implantation, the embryos increased secretion of human chorionic gonadotropin (hCG), a biochemical marker used in pregnancy tests to confirm pregnancy, and other pregnancy-associated proteins.
Dr Rugg-Gunn said: “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.”
Furthermore, the system supported post-implantation development of the embryo, enabling the analysis of embryo stages (12-14 days post fertilisation) that have been largely unexplored. The researchers observed that implanted embryos reached several developmental milestones, such as the appearance of specialist cell types in the embryo and also the establishment of precursor cell types important for the development of the placenta.
Using single cell analysis of implantation sites, the researchers were able to profile cells at the interface between the embryo and endometrium model, effectively listening in to the molecular communication between the tissues. Their results provide new insight into the complex interactions between the embryo and endometrial environment that underpin embryo development immediately after implantation.
Dr Irene Zorzan, co-first author of the study and postdoctoral fellow, explained the impact of the model to this field of research: “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”.
A pathway to understanding personal explanations for infertility
In addition to extending our textbook understanding of development at this crucial stage, the team’s model could be used to detect differences in the endometrial response in the embryo-womb lining communication for individuals experiencing infertility issues and also to test treatments that may increase reception of the embryo by the endometrium.
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.”
Publication reference: Molè et al. (2025). Modelling human embryo implantation in vitro.
Press contact
Honor Pollard, Communications Manager, Babraham Institute
honor.pollard@babraham.ac.uk
Header image description: Microscopy image of a day 14 human embryo that has implanted in the new endometrial model. The bright blue cells in the centre of the image are unspecialised epiblast cells that later in development form all of the tissues of the body. The orange-coloured cells are trophoblast cells that will later form the placenta. The blue cells surrounding the embryo are endometrial cells that support embryo implantation and growth. Credit: image taken by Matteo Molè at the Babraham Institute.
Research funding
This research was supported by strategic funding to the Institute from BBSRC in addition to funding awarded to Peter Rugg-Gunn from the MRC and Welcome Trust. Irene Zorzan is funded by a Leverhulme Early Career Fellowship.
About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
About BBSRC
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
17 December 2025