Modeling human embryo implantation in vitro
Implantation of a human embryo into the endometrium is a crucial event in gestation, as it marks the initiation of a pregnancy and is prone to high failure rates. We have limited understanding of these stages because of the inaccessibility of implanting embryos and the lack of suitable model systems. Here, we establish an in vitro model that recapitulates the luminal, glandular, and stromal compartments of the superficial layer of receptive human endometrium. Human embryos and blastoids implant into the endometrial model, achieving post-implantation hallmarks including advanced trophoblast structures that underlie early events in placental development. Single-cell RNA sequencing of the embryo-endometrial interface at day 14 uncovers predicted molecular interactions between conceptus and endometrium. Disrupting signaling interactions between extravillous trophoblast and endometrial stromal cells caused defects in trophoblast outgrowth, demonstrating the importance of crosstalk processes to sustain embryogenesis. This platform opens the opportunity to investigate early stages of human embryo implantation.
Authors
- Mina Vasilic
- Christopher A. Penfold (ORCID: https://orcid.org/0000-0001-5823-4705)
- Ruth B. Lathi (ORCID: https://orcid.org/0000-0003-2159-2714)
- Sarah Elderkin (ORCID: https://orcid.org/0000-0003-4861-8638)
- Peter J. Rugg‐Gunn (ORCID: https://orcid.org/0000-0002-9601-5949)
- Simon J. Cook (ORCID: https://orcid.org/0000-0001-9087-1616)
- Anastasia Mania
- Stephen Harbottle
- Sara Morales-Alvarez (ORCID: https://orcid.org/0000-0002-1324-2872)
- Andrea Palomar (ORCID: https://orcid.org/0000-0003-0106-7250)
- Alexandra Pokhilko (ORCID: https://orcid.org/0000-0001-6565-6551)
- Rachel Gibbons
- Kathryn Balmanno (ORCID: https://orcid.org/0000-0002-6417-3889)
- Alexander R. Dunn (ORCID: https://orcid.org/0000-0001-6096-4600)
- Alicia Quiñonero (ORCID: https://orcid.org/0009-0000-7286-5757)
- Charalampos Androulidakis (ORCID: https://orcid.org/0000-0002-5264-1841)
- Matteo A. Molè (ORCID: https://orcid.org/0000-0001-7342-4849)
- Afshan McCarthy (ORCID: https://orcid.org/0009-0005-5450-8496)
- Lauren Weavers
- Nicole Horsley (ORCID: https://orcid.org/0000-0002-2712-2388)
- Anneliese Jarman
- Ridma C. Fernando
- Irene Zorzan (ORCID: https://orcid.org/0000-0002-9229-5293)
- Lusine Aghajanova (ORCID: https://orcid.org/0000-0002-3515-9252)
- Kathy K. Niakan (ORCID: https://orcid.org/0000-0003-1646-4734)
- Katie Heywood (ORCID: https://orcid.org/0000-0002-7015-5783)
- Roberto Yagüe-Serrano
- Francisco Domı́nguez (ORCID: https://orcid.org/0000-0002-7620-8081)
- Amparo Mercader
- Jhanavi Srinivasan
- Paul Serhal
- Max Polanek
- Anthony Hoa Bui
- Tereza Cindrova-Davies
- Lucy Laurier
- Suzanne Cawood
- Molika Sinha
- Immaculada Sánchez-Ribas
- Pilar Alamá
- Richard Acton
- Ippokratis Sarris
- Yang Wang
- Graham J. Burton
- Adam Bendall
- Srividya Seshadri
- Liesl Nel-Themaat
Institutions
- Babraham Institute (GB)
- University of Cambridge (GB)
- Fetal Medicine Foundation (GB)
- MRC Centre for Reproductive Health (GB)
- King's College Hospital (GB)
- The Centre for Reproductive & Genetic Health
- King's Fertility
- Friedrich Miescher Institute (CH)
- Stanford University (US)
Publication Details
- Journal
- Cell
- Published
- 2025-12-23
- DOI
- https://doi.org/10.1016/j.cell.2025.10.027
- Citations
- 7
- Primary Topic
- Reproductive System and Pregnancy
- Type
- article
- Field-Weighted Citation Impact
- 5.58