A woman is born with all the eggs she will ever have, and each one must remain dormant for decades before finally completing a specialised cell division called meiosis just before ovulation. This process is error-prone, and those errors are the single biggest reason fertility plummets after age 40. Yet the molecular mechanisms that keep eggs healthy during their long arrest, and that later control the final chromosome-splitting step, remain poorly understood. This project uses mouse eggs to dissect those mechanisms at the molecular and cellular level. The work is fundamental science — it will not produce a fertility treatment tomorrow. But understanding how meiosis is controlled could eventually point to ways to reduce chromosome errors in older eggs, potentially lowering miscarriage rates and improving outcomes for women who conceive later in life. Similar fundamental research on cell division has already led to cancer therapies and insights into developmental disorders.
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The ability to produce a healthy fertile egg is essential for reproduction. Problems associated with the development of eggs are a major cause of infertility and early embryo loss (miscarriage). One of the reasons why eggs are so vulnerable is that they go through a specialised process known as meiosis. This process starts during foetal life and does not finish until after the egg is fertilized; more than 40 years later in some cases. Furthermore, women are born with all the eggs that will be available for her reproductive lifespan; no new eggs can be made. In meiosis the egg stops and starts at different stages but spends most of its life in a so-called ?dormant? state in the ovary. At some point the egg starts to grow increasing in diameter by 5 fold and in volume by about 300 fold to become one of the largest cells in the body (one-tenth of a millimetre across). Through all of this process the egg remains arrested in development and it is not until just before ovulation that the egg continues meiosis and halves the number of chromosomes. This meiotic division is prone to errors and is the single main reason why there is such a dramatic decrease in fertility as women get older, particularly over the age of 40. We are using mouse eggs to try to understand how meiosis works so that we can understand more about how to keep eggs arrested and healthy in the ovary and how they can go through the meiotic division without errors that cause poor quality embryos. Advances in our research are communicated in scientific journals, specialist websites and by press releases to the mainstream media. This way we aim to keep scientists, those with special interest and the public aware of our MRC funded research.
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