Life Sciences Research for Lifelong Health

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News

Babraham research provides new insights into factors ensuring a healthy pregnancy

Researchers at the Babraham Institute and University of Cambridge have made a breakthrough in understanding how the interplay between the foetus and the maternal immune systems ensures a healthy, successful pregnancy. This new understanding of the fundamental biology behind interactions between the placenta and the immune system may provide insight into the basis of human pregnancy disorders such as recurrent miscarriage, pre-eclampsia and foetal growth restriction, with potential prospects for intervention. The developmental processes occurring during pregnancy are something of an immunological puzzle. The foetus and the placenta are to some extent considered ‘foreign’ by the mother’s body, as they produce paternal proteins (antigens) that should provoke an immune response by the mother. However, instead of rejecting the foetus, the mother’s immune system recognises and tolerates the paternal antigens, harnessing the immune interaction to promote foetal development. The research, published today in Proceedings of the National Academy of Sciences of the United States of America (PNAS), reveals that the father’s genes instruct the maternal immune cells on how to build the best resources in the uterus for the developing foetus - remodelling the blood supply to optimise foetal nourishment - and safeguard the foetus from rejection. “This paradox has puzzled scientists for decades and understanding how the foetus evades rejection, except in severe pregnancy complications, has remained elusive,” said Dr Myriam Hemberger of the Babraham Institute, an institute which receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), and joint senior author with Dr Francesco Colucci, formerly at Babraham and now at the University of Cambridge. “Our findings show that paternal antigens on foetal trophoblast cells, which form the placenta and are therefore in direct contact with maternal tissue, help to transform the uterus for robust placental and foetal growth. This is essential for reproductive success.” The research reveals that specific combinations of genes from the father’s immune system, and their target receptors on maternal immune cells, favourably affect blood supply and growth of the foetus. Natural Killer (NK) cells are white blood cells that defend us from tumours, viruses and other assaults on our immune system. However, a specialised set of NK cells in the uterus (uNK), plays a key role at the maternal-foetal boundary when a fertilised embryo implants, adapting the uterine blood vessels to nourish the foetus. Paternal immune genes (MHC) in the placenta provide information to uNK cells to ensure that the foetus receives enough blood. The mouse model used in this research, which has direct analogy to human pregnancy, will provide better understanding of the precise factors and pathways that are important for a healthy pregnancy and optimal intrauterine development. Pre-eclampsia, a disorder occurring in as many as 5% of pregnancies, is associated with problems with blood vessel development in the uterus. Certain associations between maternal uterine NK cells and paternal MHC signatures have been linked with a likelihood of developing pre-eclampsia and recurrent miscarriage, as shown by Prof Ashley Moffett at the University of Cambridge who is also a collaborator in this study. Not only is the interaction of specific genes in the immune system key for foetal programming, but also has direct relevance for life-long health and wellbeing since adult diseases like diabetes and hypertension are known to have early developmental origins. “What is most exciting,” says Dr Colucci now at the University of Cambridge Department of Obstetrics and Gynaecology, “is that by revealing the similarities between human and mouse immunology during pregnancy, the research lays new foundations for using mouse genetics to test new ideas and hypotheses informed by human genetics data.” The Babraham Institute undertakes world-leading life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. The work was supported by a Babraham Institute Synergy Award to Drs. Colucci and Hemberger, the BBSRC, the Centre for Trophoblast Research at the University of Cambridge, the MRC and the Wellcome Trust. Contact The Knowledge Exchange Office Email:  kec@babraham.ac.uk Tel:       +44 (0)1223 496206 Dr Myriam Hemberger (BI) Email: myriam.hemberger@babraham.ac.uk The Babraham Institute Babraham Research Campus Cambridge CB22 3AT United Kingdom Publication details: Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M (In press) Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proceedings of the National Academy of Sciences of the United States of America http://dx.doi.org/10.1073/pnas.1005342108 Further information about the publication and the lead author can be found here Notes to Editors: 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. (www.babraham.ac.uk) 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: www.bbsrc.ac.uk For more information about BBSRC strategically funded institutes see: www.bbsrc.ac.uk/institutes The Centre for Trophoblast Research The Centre for Trophoblast Research is an inter-departmental initiative that aims to promote the study of placental biology, with special reference to the trophoblast, both within and outside Cambridge. The centre, which draws together researchers from Babraham, The Department of Physiology, Development and Neuroscience, The Gurdon Institute and Addenbrookes Hospital, was officially launched in July 2008 and aims to facilitate interactions and collaborations between established researchers, both nationally and internationally. The Centre aims to promote research and teaching in placental biology and the developmental origins of the trophoblast within the University of Cambridge and affiliated institutes through Next Generation Research Fellowships, Graduate Studentships, seminars, workshops, and infrastructural support. One of the Centre’s principal aims, however, is to encourage young investigators into the field and foster their careers.  http://www.trophoblast.cam.ac.uk/

Posted

7 February, 2011