Life Sciences Research for Lifelong Health

Babraham epigenetics research paves the way for a better understanding of unexplained infertility

Scientists at the Babraham Institute have made a breakthrough in understanding how mammalian genomes are modified in the egg and sperm and are reprogrammed after fertilisation, which also has implications for better understanding fertility. Around 15% of couples worldwide have difficulty conceiving a child and in around 5% of cases the reasons for infertility remain elusive. Attention is now turning to epigenetic changes, which are important regulators for many biological processes including the development of sperm and eggs. This research, in collaboration with the National Institute for Child Health and Development in Tokyo, may bring new understanding to cases of infertility where there is no obvious underlying cause and pave the way for improvements in diagnosis of infertility and Assisted Reproductive Technologies (ART) in humans. At the heart of embryonic reprogramming are chemical changes (methylation) to the genome, which influence gene expression without altering the genetic sequence, yet can be inherited. Methylation marks are one of the ways that genes get switched on or off in different places at different times, enabling different tissues to develop from a single fertilised egg. If these ‘epigenetic’ methylation marks are not copied correctly from the egg and sperm in the developing embryo, mistakes could be retained for the individual’s lifetime, potentially leading to errors in epigenetic patterns and human disorders. The research, reported in the August edition of the journal Nature Genetics, details for the first time a genome-wide methylation map of mammalian oocytes (eggs), which will provide scientists with a greater understanding of how we develop into healthy individuals and maintain wellbeing during ageing. Dr Gavin Kelsey, senior author of the paper and a Group Leader at the Babraham Institute, which receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) explained, “A greater understanding of how methylation landscapes are set up has far reaching implications not only for understanding mechanisms of inheritance and development but also our susceptibility to age-related diseases since conditions like heart disease, diabetes and obesity may be associated with errors in epigenetic regulation. “The research may also bring new insight to reproductive problems, helping to pinpoint some of the epigenetic impairments suspected to underlie infertility where there is no obvious cause. This research lays the foundations for understanding post-fertilisation reprogramming of embryos and may contribute knowledge to improve assisted reproductive technologies in humans.” This research also brings new understanding of epigenetic regulation and ‘genomic imprinting’ in mammals, a process where particular genes are used depending on whether they come from the mother or father. Central to this are ‘epigenetic’ methylation tags, which modify DNA structure and appear to give the chromosomes a ‘memory’ of their parental origin.  Major epigenetic reprogramming occurs in germ cells (eggs and sperm) to erase and reset parental imprints and in early pre-implantation development. After fertilisation, methylation is extensively reprogrammed in the developing embryo, except at imprinted genes which have to retain the methylation tags inherited from the egg or sperm. If one copy of a gene is epigenetically ‘turned off’ and the remaining working gene has a mutation, problems may arise.  A number of imprinting diseases have been reported in humans and animals born after the use of ART, although their incidence remains low - for example, a loss of methylation of the mother’s copy of a certain gene leads to Beckwith-Wiedemann syndrome, an over-growth disorder with a higher risk of developing childhood cancer. Consequently understanding more about the methylation landscape of mammalian eggs and early embryos may help inform strategies for assisting with human reproduction and may lead to new possibilities in pre-implantation genetic diagnosis. This landmark methylation map of germ cells and embryonic development may also have implications for the assisted reproduction of livestock. It will also be an invaluable resource for the research community, which will enable scientists to determine how much of the genome is imprinted, bringing greater understanding about the regions of the genome that are resistant or prone to methylation and the role of this in mammalian development. This research was supported by the Babraham Institute, which undertakes international quality life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health, the BBSRC and also was supported by grants from The Medical Research Council and the Centre for Trophoblast Research in Cambridge. Contact The Knowledge Exchange Office Email: Tel:       +44 (0)1223 496206 Dr Gavin Kelsey, Group Leader, Epigenetics Laboratory Email: The Babraham Institute Babraham Research Campus Cambridge CB22 3AT United Kingdom Publication details: Dynamic CpG island methylation landscape in oocytes and preimplantation embryos Sébastien A Smallwood, Shin-ichi Tomizawa, Felix Krueger, Nico Ruf, Natasha Carli, Anne Segonds-Pichon, Shun Sato, Kenichiro Hata, Simon R Andrews & Gavin Kelsey Nature Genetics DOI The Babraham Institute The Babraham Institute, which receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), undertakes international quality life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. The institute received £22.4M investment from BBSRC in 2010-11. The Institute’s research provides greater understanding of the biological events that underlie the normal functions of cells and the implication of failure or abnormalities in these processes. Research focuses on signalling and genome regulation, particularly the interplay between the two and how epigenetic signals can influence important physiological adaptations during the lifespan of an organism. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and healthier ageing. ( About BBSRC The Biotechnology and Biological Sciences Research Council (BBSRC) invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. Funded by Government, and with an annual budget of around £445M, we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals. For more information about BBSRC, our science and our impact see: For more information about BBSRC strategically funded institutes see:


18 August, 2011