Graham Burton FMedSci
Professor of Reproductive Biology Tel: +44 (0)1223 333856, Fax: +44 (0)1223 333840, E-mail: gjb2@cam.ac.uk
Placental
development and function
Research Summary:
My focus is on human early placental development, and the involvement
of the placenta in complications of pregnancy such as miscarriage, intrauterine
growth restriction and pre-eclampsia. In particular, we are interested
in the effects of oxygen, hypoxia, and oxidative and endoplasmic reticulum
stress on trophoblast differentiation and function at the molecular and
cellular levels. By understanding these at the basic science level, we
aim to develop novel therapeutic interventions to improve outcome in complicated
pregnancies.
Key advances of the group:
2000 – Confirmed, in collaboration with Prof Eric Jauniaux, that
the maternal arterial circulation to the placenta is not fully established
in normal pregnancies until the end of the first trimester. We demonstrated
that the oxygen concentration rises three-fold within the placenta at
10-12 weeks of gestation, and that this poses an oxidative challenge to
the placental tissues. Furthermore, we showed that early onset of the
maternal circulation is associated with spontaneous miscarriage.
2001 – Proposed concept of ischaemia-reperfusion injury to the placenta
as the precipitating insult in the pathophysiology of early-onset pre-eclampsia.
2002 – Identified histiotrophic nutrition to the conceptus during
the first trimester of pregnancy.
2003 – Proposed the concept that villous regression and remodelling
at the end of the first trimester is induced by locally high levels of
oxidative stress associated with onset of maternal blood flow.
2004 – Pioneered the application of stereological techniques to
quantify the structure of the murine placenta.
2005 – Identified that phylogenetically old carbohydrate metabolic
(polyol) pathways are highly active during the first trimester when the
intraplacental oxygen concentration is low.
2006 – Demonstrated that fetal cell-free DNA is released from the
placenta through apoptotic pathways.
2007 – Demonstrated that labour induces oxidative stress and transcriptional
changes in the placenta that mimic those seen in pre-eclampsia.
2008 – First identification that endoplasmic reticulum stress contributes
to the placental pathophysiology of intrauterine growth restriction.
2009 – Demonstrated that a proportion of the nuclei within the syncytiotrophoblast
are transcriptionally active.
2010 – Identified a transcriptional network that may define a trophoblast
stem cell population within the placenta.
Awards, Honours
2001 – International Spa Foundation Prize (with Prof E Jauniaux) for
research on "The role of placental oxygenation and generation of free radicals
in the pathogenesis of miscarriages and preeclampsia".
2005 – FEDERA Award from the Dutch Federation of Medical Scientific
Societies for research on "The maternal-fetal interface in early human
pregnancy".
2007 – Appointed inaugural Director of the Centre for Trophoblast Research.
2008 – Elected European Editor of Placenta.
2011 – Elected FMedSci.
Colleagues
Prof Eric Jauniaux (University College Hospital, London)
Dr Stephen Charnock-Jones (University of Cambridge)
Prof Anne Ferguson-Smith (University of Cambridge)
Dr Andrew Murray (University of Cambridge)
Prof John Kingdom (University of Toronto)
Dr Jeremy Skepper (University of Cambridge)
Dr Tereza Cindrova-Davies (Research Associate)
Dr Billy Yung (Research Associate)
Mr Arjun Jain (Graduate Student)
Ms Norah Fogarty (Graduate Student)
Ms Melanie Monk (Research Technician)
Main sources of funding
Wellcome Trust Programme grant, Anatomical Society, Action Medical Research, MRC, Evelyn Trust
Recent publications
Papers:
Hemberger, M., Udayashankar, R., Tesar, P., Moore, H. and Burton, G.J. (2010)
ELF5-enforced transcriptional networks define an epigenetically regulated
trophoblast stem cell compartment in the human placenta. Hum Mol
Genetics, 19,
2456-2467.
Burton, G.J., Jauniaux, E. and Charnock-Jones, D.S. (2010). The influence of the intrauterine environment on human placental development. Int J Dev Biol, 54, 303-312.
Burton, G.J. (2009) Oxygen the Janus gas; its effects on human placental development and function. J Anat, 215, 27-35.
Burton, G.J., Woods, A.W., Jauniaux, E. and Kingdom, J.C.P. (2009) Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta, 30, 473-482.
Yung, H-W, Calabrese, S., Hynx, D., Hemmings, B.A., Cetin, I., Charnock-Jones, D.S. and Burton, G.J. (2008) Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction. Am J Pathol, 173, 451-462.
Books:
The Placenta and Human Developmental Programming. (2010) Eds. Burton, G.J.,
Barker, D.J.P., Moffett, A. and Thornburg, K. Cambridge University Press,
Cambridge, pp. 246.
Comparative placentation; structures, functions and evolution. (2008) Wooding, P. and Burton, G.J. Springer, Berlin, pp. 301.
Above: Placental villi from a normal term placenta showing increased levels of oxidative stress following exposure to hypoxia-reoxygenation in vitro. The syncytiotrophoblast covering of the villi shows co-localisation (orange) of hydoxynonenal (green), a marker of lipid peroxidation, and the vasoconstrictor, endothelin (red). Nuclei are stained by DAPI (blue). Placental oxidative stress is thought to be a key mediator in the development of pre-eclampsia, stimulating the release of factors that cause maternal endothelial cell activation. Image courtesy of Dr Cindrova-Davies.
Above: The microvasculature of a terminal villus from a mature human placenta outlined by a fluorescent dye that binds to the fetal endothelial cells. Nuclei of the overlying syncytiotrophoblast are stained by DAPI (blue). The complex branching and localised dilations of the capillaries ensures efficient exchange between the maternal and fetal circulations. Image courtesy of Dr Skepper.