Novel in vitro endometrial scaffolds to investigate embryo implantation and early development

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The overarching scientific goals of this project are to demonstrate the accurate physiology of human endometrial scaffolds that we have recently developed, and to establish the ability of this new model to support the implantation and early development of embryo-like models created from human, marmoset and mouse pluripotent stem cells.Our vision is that this new in vitro implantation model will overturn the need to use animals in experiments to study implantation and early embryogenesis. This will achieve the 3Rs goal of this project and in doing so will contribute to the mission of the NC3Rs by replacing animals and reducing the number of animals used in research.The four specific objectives of this project are:1) Obtain reference data sets of human embryo development with the in vitro implantation system, which will be used to benchmark the data collected in Objectives 2 and 3.2) Investigate the ability of stem cell-based human embryo models called blastoids to develop within the endometrial scaffold.3) Determine the ability of blastoids made from existing mouse and marmoset pluripotent stem cell lines to implant and develop in the human endometrial scaffold system.4) Create a comprehensive resource and training programme to maximise the uptake of our new models.All current studies on embryo implantation and early development in humans and other species use animals. This is because there are no suitable in vitro models that can provide a better, alternative approach to investigate these key processes. Our project is important because it will provide the first physiologically-relevant in vitro model to study embryo implantation and early development. Here, we will demonstrate the accuracy and reproducibility of this system and we will develop suitable means to ensure the broad uptake of this animal-free system to other researchers. More generally, the successful establishment of this complex, multi-tissue human cellular system will encourage and provide a framework to help the development of other in vitro models to study additional physiological processes that could replace the use of animal in those other fields.The project has a high chance to succeed because the research team already have the endometrial model up and running, thereby completing the riskiest aspect of the work. The close physical proximity of the two research teams, their frequent interactions, and the world-class training and research environments of their host institutes collectively support the likelihood of a successful project outcome.