A team of researchers has developed a bioengineered endometrial model to study crucial yet poorly understood scientific processes: embryo implantation, which determines whether a pregnancy continues, and the initial communication with the mother. On Tuesday, the journal Cell described in a scientific article how the first artificial uterine lining was designed to respond to embryo implantation in the same way as the human endometrium during pregnancy, producing the essential mechanisms to 'nourish' it. This work is the result of a collaboration between scientists from the Babraham Institute in Cambridge (United Kingdom) and Stanford University in the United States. The developing embryo implants into the uterine lining (endometrium) one week after fertilization, marking one of the least scientifically understood stages due to the difficulty of observing the embryo during and after implantation. 'Understanding embryo implantation and its development immediately afterward has significant clinical relevance, as these stages are particularly prone to failure, especially in in vitro fertilization (IVF) processes,' explains one of the authors, Peter Rugg-Gunn, a researcher at the Babraham Institute. The engineering behind the artificial endometrium To achieve this understanding, Rugg-Gunn and his team successfully replicated the complex physiological properties and cellular composition of the uterine lining in three dimensions (3D). The scientists isolated two essential types of cells from endometrial tissue donated by healthy individuals who had undergone biopsies to artificially recreate this tissue: epithelial and stromal cells. Simultaneously, they used information from the donated tissue to identify the key components that give structure to the uterine lining. The researchers incorporated these components, along with the stromal cells, into a special gel to promote cell growth into a thick layer. Subsequently, they added epithelial cells that spread over the stromal cells. The artificial endometrium achieved the same cellular architecture as the donated tissue and responded identically to hormonal stimulation, indicating it could be receptive to embryo implantation, the authors explain. The team tested their model using early-stage human embryos donated by individuals who had undergone IVF procedures and discovered that the embryos went through the expected stages of adhesion and implantation in the artificial endometrium. After implantation, the embryos increased their secretion of certain proteins characteristic of pregnancy and human chorionic gonadotropin (hCG), which is used in pregnancy detection tests. 'We were excited to see that our system released the essential factors necessary to nourish the embryo during the first weeks of pregnancy.' 'Previous models had not been able to achieve this, so this has been a tremendous breakthrough,' states Rugg-Gunn in a press release. The artificial endometrium supported embryo development after implantation, enabling the analysis of the earliest embryonic stages (12-14 days after fertilization), which have until now been virtually unexplored. The first mother-child communication The researchers observed that embryos implanted in the artificial endometrium reached several developmental milestones, such as the appearance of specialized cell types and the establishment of others that are precursors to placental development. Individual cellular analysis at the implantation sites allowed them to discover the first 'cellular communication' between the embryo and the endometrium, creating the structures through which a mother and child exchange oxygen and nutrients during pregnancy. Better understanding this stage, Rugg-Gunn emphasizes, is key to finding answers about infertility, miscarriages, and conditions like preeclampsia. 'We are immensely grateful to the people who donate surplus embryos,' concludes another of the authors, Sarah Elderkin, from the Babraham Institute. 'Now we will be able to better understand the first moments of embryonic development and better understand how that first synchronized communication between mother and baby occurs, which is fundamental for both to remain healthy.'
