Studying factors supporting human embryo development in culture

The goal of our research project is to understand how the major cell lineages are formed as the early human embryo develops, implants and grows.

We are particularly interested in a developmental window spanning from just before the embryo has implanted until shortly after it implants. This period is critical for the establishment of a healthy embryo and successful pregnancy. Almost half of all human embryos fail to progress past this stage, resulting in a high rate of pregnancy loss, and a substantial health burden for patients with recurrent miscarriages. By studying the contribution of genetic and epigenetic factors to the formation of early embryo cell types, and by identifying biomarkers of healthy pregnancies, we aim to better understand the processes required for embryo development. Ultimately, we hope that this information will help to improve IVF outcomes and potentially identify causes of infertility in patients.

We use only surplus embryos that have been donated by patients undergoing IVF treatment. These embryos were previously frozen as part of routine IVF cycles. Patients who no longer require their embryos for their treatment can consent to donate them to our research programme. The project is approved by an NHS National Research Ethics Committee and performed under a Research Licence issued by the Human Fertilisation and Embryology Authority (HFEA) (project number R0209-1-a). The research is carried out at the Babraham Institute (licenced centre 0370) and led by Dr Peter Rugg-Gunn.

 

Figure

The figure above shows a schematic of how the human embryo on day six after fertilisation attaches to the endometrium, implants, and continues to develop over the next eight days. A goal of our research is to develop an advanced culture system that can mimic the endometrium and is able to sustain the faithful development of human embryos up until day 14. Achieving this would allow us to examine the key changes in genetic and epigenetic factors that instruct the formation of the different cell lineages of the human embryo at the stage, which is necessary for the establishment of a healthy pregnancy.

 

Purpose of our research project:

This project aims to study the early phases of human embryo development. We hope that the results of these studies will benefit medical knowledge in several important ways, such as:

  • Improving our understanding of how human embryos develop. Establishing an advanced in vitro culture system with endometrial tissues to help support the development of early stage embryos would open up the possibility of investigating the process of embryo implantation in cellular and molecular depth. In particular, we plan to investigate how genetic and epigenetic factors contribute to the specification, development and function of embryonic and extraembryonic cell lineages during this critical stage of development. This knowledge will provide important new insights into the gene activity and their regulatory networks underlying successful implantation and post-implantation development of the human embryo.
  • Promoting advances in the treatment of infertility. Following assisted conception treatments, it is estimated that 30-60% of embryos fail to complete implantation and do not develop beyond this stage, resulting in pregnancy failure and spontaneous abortion. This pre-clinical loss is one of the main factors causing the low efficiency of IVF procedures. In our prior work, we have identified a set of signalling factors that might help support healthy development of the embryo past the implantation stage. One objective of our research is to test whether providing these factors in culture could enhance embryo survival, support implantation in vitro and promote heathy development of the embryo post-implantation. This information would provide an important first step for devising new therapeutics with the aim to overcome implantation failure and promote heathy pregnancy. Increasing the success of human embryo development at implantation could help in the future to overcome the clinically observed implantation barrier, to reduce the percentages of early pre-clinical losses, and to ultimately increase the success rates of pregnancies leading to live births following IVF procedures.
  • Increasing knowledge about the causes of miscarriage. The transition from pre-implantation to early post-implantation is a critical stage of human embryogenesis. Failure of the embryo to implant in the maternal womb and progress with development is one of the major factors behind early pregnancy losses. The interactions between the embryo and endometrium established at this stage have not been examined in molecular detail. In our research project, we aim to recreate the maternal environment by engineering a new system comprising of endometrial cells. By culturing embryos on this endometrial tissue system, we will study the molecular interactions established at implantation between the embryo and the maternal environment. This system will enable us to investigate the molecular causes of miscarriage by using endometrial samples from patients with recurrent pregnancy loss. These experiments are expected to provide important new insights into what goes wrong between the endometrium and embryo leading to implantation failure, thereby uncovering molecular causes behind early pre-clinical miscarriage.

 

The information on this page is intended for patients undergoing IVF who may be interested in donating their surplus embryos to our research programme. We currently collaborate with the following clinics:

The Patient Information Document provided to you by the clinic will have a detailed description and information on donating embryos to research and to the projects carried in our centre.

If you would like to receive counselling or discuss the possibility of donating embryo to this project, please contact your treatment clinic and they will be able to provide you with an independent counsellor, the Patient Information Document related to this project and the Research Consent Form.

If you would like to receive further details on the project, please contact the principal investigator of the research study: Dr. Peter Rugg-Gunn

 

Funding:

This project is funded by the Wellcome Trust, the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC).

A complete list and summaries of embryo research projects taking place in the UK can be found: https://www.hfea.gov.uk/donation/donors/donating-to-research/embryo-research-project-summaries/