Eggs and sperm pass on more than just DNA—they carry chemical tags that tell genes when to switch on or off, and some of these tags persist after fertilisation to shape how the embryo grows. This matters because a special class of these tags, called imprinted genes, are set differently in eggs and sperm, and they control crucial processes like placenta development and fetal growth. If these tags are placed incorrectly, it can lead to fertility problems or developmental disorders. Yet scientists do not fully understand how the tags are established in egg cells or how the embryo remembers them. The researchers will use mouse models to modify epigenetic marks and study their effects in eggs and very early embryos—tissues that are inaccessible in humans. They have also developed sensitive techniques to read all the epigenetic marks in single human cells, allowing them to trace differences in embryos back to the eggs they came from. If this fundamental research succeeds, it could reveal whether certain epigenetic patterns in eggs are diagnostic for fertility problems. That would give clinicians a new way to assess egg quality without relying on trial and error.
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Although we inherit 22 chromosomes from each of our parents, the egg and the sperm pass on more than the bare DNA sequence. The DNA sequence and the chromosomes themselves are modified by numerous chemical tags - call epigenetic marks - that are vital for specifying which genes should be active and which silent in any cell in our body. Where these epigenetic marks are placed on the DNA is constantly being modified as cells develop and differentiate into different tissues. It is also crucial that most epigenetic marks that were present in the egg and sperm are removed at fertilisation, so that the programme of gene expression for development of the embryo can be kick started correctly. However, some epigenetic tags can persist throughout our lifetimes, and some even remain as a permanent memory of whether a gene came from the egg or sperm. As a result of this special class of tags, some genes exhibit different activities of the copy inherited from mothers and the copy from fathers. These are referred to as "imprinted genes", because they are imprinted differently in the sperm and egg. Imprinted genes are particularly important for the normal development of the placenta and for how the fetus grows. We are trying to understand how imprinted genes are epigenetically tagged during the development of egg cells and how these tags are remembered as the embryo develops. It seems that different types of epigenetic tags are involved - some directly on DNA, some on the chromosome structure - and some marks will end up more important in the embryo itself whereas others will be more influential in the placenta, which nonetheless can control how the baby grows and develops. Much of the work we propose will be conducted in mouse models, where we can modify the epigenetic marks on genes, or the activity of genes, and we can access tissues - egg cells and very early embryos - in a way that we cannot do so with human samples. Some of our work uses very sensitive techniques we have developed that can read all the epigenetic marks in individual cells. We are now using these techniques to understand if there is variation in epigenetic marks in human embryos before they implant. We believe that some differences can be traced back to the eggs from which the embryos developed, leading us to propose that some epigenetic changes could be diagnostic for problems in fertility.
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