University of Manchester and St Mary’s Hospital
This project involves studying early human embryo development. The researchers want to find out what factors contribute to normal embryo development, and what happens when development goes wrong. They will be assessing the impact of sperm DNA damage and factors which might affect embryo development and implantation into the womb, including the culture environment and the effect of freezing embryos.
It is necessary to use human embryos for this research as although important information has come from studies of animal embryos, they develop differently to human embryos.
MRC Human Genetics Unit, Edinburgh
Embryonic stem (ES) cells were first identified in mouse embryos in 1981. Cells similar to ES cells can be made by manipulating differentiated cells (for example skin or nerve cells) to make ‘induced pluripotent cells’ (iPS) cells.
ES and iPS cells have the unique ability to turn into any tissue in the body. ES and iPS cells can now also be obtained from human embryos and adult tissues. However, human stem cells are not as consistent and reliable as mouse stem cells. In this project, human and mouse embryos are compared with the aim of developing ways to improve human ES cells so that they’re easier to grow and can differentiate into wider range of tissues.
By using specially optimised culture conditions for human ES cells, they can be instructed to form structures resembling blastocysts, called ‘blastoids’, comprising trophectoderm, epiblast and hypoblast. Blastoids can be generated in large numbers, enabling us to test effects of appropriate chemicals, or genetic variation on their development over the next few days.
The Francis Crick Institute
This research is concerned with early human embryo development. It is hoped that the results of these studies will benefit medical knowledge in a number of important ways.
Firstly, by improving understanding of the conditions that are important for growing human preimplantation embryos in a petri dish. These insights can hopefully lead to improvements in the treatment of infertility.
Secondly, by improving our understanding of how early human embryo cells become more specialised during early development. The first critical step in this process is when a small subset of cells are set aside to eventually form the foetus, whilst another subset of early cells differ in their fate to become the placenta (which supports the development of the foetus throughout the pregnancy). The researchers will be trying to find out how these specialisation events occur and are regulated before implantation. Understanding the genes that are essential for this first important specialisation process could provide insight into some causes of pregnancy failures and birth defects. Understanding this important switch in cell fate may also provide a deeper understanding of stem cell formation.
Lastly by developing stem cell lines that can be taken out of the embryo and multiplied in the laboratory for many years. This can help to study and better understand devastating human diseases at the cellular level in the laboratory and potentially develop new drug treatments.
Physiology Laboratory, University of Cambridge
A high proportion of natural abortions occur because of developmental failure as the embryo implants into womb. To avoid such failures in the IVF clinic, it would be helpful to know what an embryo must achieve during the initial days when it is placed in the mother’s womb. This project involves culturing embryos in an in vitro (artificial) environment that has been shown to permit the correct development of an embryo until day 13.
For the first-time this allows researchers to study human embryo development from day 7 to day 13, a period that normally cannot be seen. This research will help in understanding the causes underlying early pregnancy loss.
Cardiff University School of Biosciences
At fertilisation, the sperm fuses with the egg and sends a calcium signal to trigger it to begin development. Without this signal, the process of fertilisation is not successful and an embryo cannot be made. In a proportion of IVF and ICSI treatments it appears that the egg fails to fertilise because of a lack of this activating calcium signal.
Previous research in mouse eggs has shown that sperm contain a protein, referred to as PLCzeta, which enters the egg during fusion and triggers the calcium changes that lead to egg activation and embryo development. This project aims to extend some of these studies to human eggs.
In this project, human eggs that have failed to fertilise during IVF treatment cycles will be injected with the PLCzeta protein to see how effective it is in stimulating the calcium changes that cause egg activation. The effectiveness of PLCzeta protein will be compared with certain chemicals that have been used by some clinics to stimulate calcium changes in human eggs that have failed to activate after ICSI treatment.
This work could provide important information on how the sperm normally triggers development during human fertilisation. It may help explain why some eggs fail to fertilise after procedures such as ICSI, and it would offer new ways to overcome such fertilisation failure.
Guys Hospital, London
This project is testing a technique involving the splitting of embryos. If successful, it could be possible to split one embryo into two, both of which will have the same genetic information. Embryos for research can be hard to obtain so by being able to split one, it reduces the number of embryos used and avoids genetic background bias.
Oxford Fertility
At fertilisation, the sperm activates the egg to begin development in a process called egg activation. A protein called PLCzeta is important in this process. If there is not adequate PLCzeta then the egg may not be successfully fertilised. Men without adequate PLCzeta may therefore be infertile. This project involves using a synthetic version of PLCzeta created in a lab and seeing if it can be used for fertilsation where there are low levels of natural PLCzeta.
The second part of this project involves using high-frequency time lapse filing to observe the tiny movements that take place in an egg during the first few hours after activation. These, and other experiments on eggs and very early stage embryos, will increase our knowledge of the processes that occur around fertilisation. In the future, the synthetic PLCzeta could be used to help in cases where there are egg activation problems, and use the time lapse technique to predict which embryos are healthier for transfer in IVF.
Institute of Reproductive and Developmental Biology Centre, Imperial College London
This project involves studying early human embryo development. From this work researchers aim to develop biomarkers that provide an indication of embryo potential. Embryo selection methods are currently based on detailed morphological parameters (structure and shape of the embryo) associated with successful IVF.
Although this morphological assessment remains the easiest way to predict embryo viability, even high-quality morphological appearances often can’t accurately predict a successful implantation. Metabolic assessment (measurement of chemical processes) of embryos may provide greater understanding and be representative of the embryo viability. This can also be done through analysis of the products left over in the culture media that the embryo is incubated in during the first few days of growth.
Laboratory methods to complete this type of assessment have been developed to become more sensitive and accurate. It is hoped these approaches will benefit understanding of early human embryo development and metabolism, and this can then lead to improved methods of embryo selection.
Centre for human development, stem cells and regeneration
There is growing evidence that the environment experienced by early embryos, for example, the way they are grown in the laboratory, or the conditions they experience in the mother’s body, can influence growth and development, both in the womb and after birth.
Such environmental conditions can make long-lasting changes to the way the embryo’s genes work. The purpose of this project is to investigate when and where a gene or its protein product are active using sensitive molecular and microscopic procedures designed for early embryos; also how this pattern influences the embryo’s growth, development and physiological functions. The parents’ body condition, for example age or BMI, will be examined to see how this affects the way the embryo grows and activates its genes, including those known to be important for making human embryonic stem cells, and whether this is influenced by the way the embryos are grown in the laboratory.
This research aims to improve our understanding of the mechanisms that regulate the embryo’s ability to develop under different conditions to maximise developmental potential whilst minimising possible risks for long-term health complications. This will have a significant impact on the treatment of infertility and inform advice given to patients.
The Babraham Institute
Our project aims to investigate the molecular factors underlying human embryo development during the transition from pre-implantation to early post-implantation. This period is characterised by major genetic and epigenetic changes that occur during the specification of embryonic and extraembryonic cell lineages and subsequent implantation of the embryo into the uterus. Furthermore, because epigenetic marks formed during this period are inherited by all subsequent foetal and adult cells, errors that arise during this early stage of development might promote the onset of certain disorders later in life, and this process is therefore important to understand in greater detail. To address these questions, we aim to optimise in vitro culture conditions to promote the accurate development of human embryos until day 14, and using this improved system we will examine changes in gene activity and epigenetic patterns in embryos from pre- to post-implantation. We will determine whether specific patterns are established differently between embryonic and extraembryonic lineages, and also in response to the interactions formed between the embryo and endometrium. Our research will identify important new insights into the processes required for healthy embryo development, which we anticipate will help to improve IVF outcomes and potentially identify causes of infertility in patients.
