Biological foundation for epigenetic investigations of ART derived human oocytes and embryos

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A growing body of evidence suggests that some of the technologies used to treat infertility in humans and/or the infertility itself may compromise the function of key genes which are associated with imprinting. The imprint is a unique mark found on a small number of genes. The imprint is established during the growth of eggs and sperm and it is vital for the development of healthy embryos before they implant to produce a pregnancy. Importantly, the imprinted mark can, in some cases, be changed erroneously during the laboratory procedures used to treat infertility. Errors in how the gene imprints are established and read may predispose an individual to diseases such as cancer and/or specific disorders associated with imprinted gene disruption including rare mental retardation syndromes such as Angelman syndrome, and Beckwith-Wiedemann syndrome. This is a major cause of concern as over a million babies have been born worldwide following assisted conception. Furthermore, it is possible that the more invasive assisted reproductive technologies (ART) which are increasingly being developed and used to treat infertile patients may predispose human embryos and the children born subsequently to imprinting errors. It is therefore of paramount importance to understand how imprinted genes work in healthy human eggs, sperm and embryos and to investigate how their programming can go wrong. This project will predominantly use highly sensitive and sophisticated molecular biology tools called microarrays and follow-up analyses to simultaneously study multiple imprinted genes and their regulators throughout the development of human eggs and embryos. The information generated by these unique studies will be used to confirm the safety of a new treatment for the in vitro growth of eggs- a technique which involves an extended period of culture in the laboratory during which time the eggs are ripened before they are fertilised. It is anticipated that status of the imprinted genes and their regulators can be used to test the safety of new ARTs, such as the in vitro maturation of oocytes, before they are introduced into routine clinical practise. The proposed work will therefore help us to understand and hopefully prevent imprinting errors and diseases being passed onto the next generation of children born following assisted conception.