- Mrs Zahraa AlYahyaei, D Phil Student
- Dr Alexandra Brooks, D Phil Student
- Dr Gavin Collett, Postdoctoral Scientist
- Ms Bec Dragovic, D Phil Student
- Dr Chris Gardiner, Postdoctoral Scientist
- Dr Jen Southcombe, Postdoctoral Scientist
- Dr Dionne Tannetta, Postdoctoral Scientist
- Reddy Aparna, Suri Sangeeta, Sargent Ian L, Redman Christopher WG, and Muttukrishna Shanthi (2009) Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia. PLoS ONE, 4(2):e4453.
- Redman C WG and Sargent I L (2009) Placental stress and pre-eclampsia: a revised view. Placenta, 30 Suppl A:S38-42.
- Zhu X M, Han T, Sargent I L, Wang Y L, and Yao Y Q (2009) Conditioned medium from human decidual stromal cells has a concentration-dependent effect on trophoblast cell invasion. Placenta, 30(1):74-8.
- Lok Christine AR, Boing Anita N, Sargent Ian L, Sooranna Suren R, van der Post Joris AM, Nieuwland Rienk, and Sturk Augueste (2008) Circulating platelet-derived and placenta-derived microparticles expose Flt-1 in preeclampsia. Reprod Sci, 15(10):1002-10.
- Lok Christine AR, Van Der Post Joris AM, Sargent Ian L, Hau Chi M, Sturk Augueste, Boer Kees, and Nieuwland Rienk (2008) Changes in microparticle numbers and cellular origin during pregnancy and preeclampsia. Hypertens Pregnancy, 27(4):344-60.
|PA||Mrs Lorraine Stayt|
|Contact address||NDOG, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, Oxfordshire, OX3 9DU, United Kingdom|
|Department||Nuffield Department of Obstetrics and Gynaecology|
The Sargent Group focuses on:
Pre-eclampsia Research: This research group has developed from a long standing collaboration between myself, Professor Chris Redman and Dr Elizabeth Linton. Our studies on the aetiology of pre-eclampsia have led us to discover that the maternal endothelial dysfunction which characterises the disease is part of a more generalised maternal systemic inflammatory response. Our hypothesis is that trophoblast debris shed into the maternal circulation is the stimulus for the inflammatory response and the cause of endothelial damage. We have shown that cellular and subcellular trophoblast fragments (micro and nanoparticles) are shed into the maternal circulation in normal pregnancy, in increased amounts in pre-eclampsia. We infer that this range of trophoblast debris is shed as a result of placental apoptosis, which is increased in pre-eclampsia as a result of oxidative stress. Our recent work indicates that trophoblast particles can be taken up by monocytes and dendritic cells and stimulate the release of pro-inflammatory cytokines. We have new evidence that suggests that the pivotal cells in this process may be NK cells rather than T cells as previously thought. This finding may provide the link between activation of the innate immune response and changes in type/type 2 immunity in normal pregnancy and pre-eclampsia.
Oxford Pregnancy Biobank: The purpose of this project is to discover new biomarkers for pre-eclampsia, which allow its early prediction and enable clinical care to be focused on the highest risk groups. This requires the analysis of blood or urine samples taken both during and prior to the development of the disease. To this end, we have established the Oxford Pregnancy Biobank to collect samples from 1,000 women a year in the 1st, 2nd and 3rd trimesters, as well as at the onset and during the disease. Placental blood flow, a partial predictor, is measured by Doppler ultrasound at the 1st and 2nd visits. Samples from the Biobank are already being used by researchers in Oxford, in other universities in the UK and overseas, as well as by industrial partners. These achievements establish a strong foundation for future translational research with respect to pregnancy problems that are a substantial economic burden on the NHS. The Biobank will enable new diagnostic biomarkers to be tested rapidly.
Cellular Micro and Nanoparticles in Pre-eclampsia: Our major focus for biomarker discovery is blood-borne and urinary microparticles (100nm -1um) and nanoparticles (exosomes, 30 nm - 100nm), which are derived from a range of cell types, including the placenta, and are significantly elevated in pre-eclampsia. Our interest in micro and nanoparticle biology in pregnancy has been linked with technical advances in particle detection, through an industrial collaboration with Nanosight Ltd (http://www.nanosight.co.uk/ ). Using Nanoparticle Tracking Analysis (NTA), we have shown that exosomes as well as larger microparticles can be reliably measured in plasma and urine, in a single analytical procedure. Changes in the levels of microparticles and exosomes are being explored as disease indicators.
Reproductive Immunology: Our group was the first to discover that extravillous cytotrophoblast expresses a unique class I antigen (later shown to be HLA-G) which plays a fundamental role in protecting the implanting embryo from maternal immune attack. This work has continued with studies of the control of trophoblast HLA-G assembly and expression, its immunosuppressive activity, and the expression of alternatively spliced forms by human embryos and their use as markers of developmental potential. Our current work focuses on type1/type2 changes in peripheral blood NK cells as possible markers of pregnancy failure in patients with failed implantation after IVF, recurrent miscarriage and pre-eclampsia.
Human Embryo Development: As Scientific Director of the Oxford Fertility Unit, I established a highly successful clinical IVF laboratory which has made possible the development of an IVF research programme. This has included developing methods for pre-implantation genetic diagnosis, studies of oocyte maturation in vitro, the assessment of embryo quality using computer “artificial intelligence” techniques, improving human embryo culture techniques by the use of growth factors. These studies lead to my becoming part of a €7.4 million European Network of Excellence to study the control of embryo implantation (EMBIC www.embic.org) which ran from 2004-2008. This network involved collaboration between 18 laboratories and 8 IVF Units from 9 European countries. I was the leader of a work package investigating immunoregulatory signals produced by pre-implantation embryos.
Sources of Funding
- Wellcome Trust 2006- 2012
Ian Sargent’s first degree was in Zoology from the University College of Wales Aberystwyth in 1974. He then studied for a PhD in Cellular Immunology in the Department of Immunology, St Mary’s Hospital Medical School, University of London, which was awarded in 1978. He joined the Nuffield Department of Obstetrics and Gynaecology, University of Oxford in 1979 as a postdoctoral scientist. He was appointed as a lecturer in 1983, promoted to Reader in 1998 and to Professor of Reproductive Science in 2004. He was Scientific Director of the Oxford Fertility Unit for nearly 20 years. He is a Fellow of Mansfield College, Oxford.
He has been an Associate Editor for Human Reproduction and the Journal of Reproductive Immunology, member of the Wellbeing of Women Research Advisory Group, Wellcome Trust Physiological Sciences Funding Committee, MRC College of Experts and a Scientific Advisory Board for the Science Foundation for Ireland. He has also been the Secretary and Treasurer for the Reproductive Immunology Group of the British Society for Immunology and is currently Treasurer for the International Society for the Immunology of Reproduction.
Awards Training and Qualifications
- 1974 Zoology, University College of Wales
- 1978 PhD in Cellular Immunology, University of London