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Prenatal programming of polycystic ovary syndrome using a clinically realistic ovine model

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Biography

Colin Duncan is a Principal Investigator in the MRC Centre for Reproductive Health at the University of Edinburgh. He is from Ayr in the South-West of Scotland and attended the University of Edinburgh. He was enthused about laboratory research while working on apoptosis with Professor Andrew Wyllie during his BSc in Pathology. He graduated MBChB with honours in 1990 followed by specialist training in Obstetrics and Gynaecology. His research training included a Wellcome Trust Clinical Training Fellowship at the MRC Reproductive Biology Unit and a Clinician Scientist and Scottish Senior Clinical Fellowship at the University of Edinburgh. He runs a research laboratory that studies polycystic ovary syndrome and normal ovarian physiology. He is a subspecialist in Reproductive Medicine and Surgery and is the lead Consultant for the Early Pregnancy Assessment Unit at the Royal Infirmary of Edinburgh and Ovulation Induction programme in the Edinburgh Fertility and Reproductive Endocrine Centre.

Current Research Interests

Large animal modelling of polycystic ovary syndrome (PCOS), the molecular correlates of its development and intervention to ameliorate its progression:

Prenatal programming using an ovine model: I am one of the few clinicians in the UK skilled in the use of clinically realistic large animal models of disease and hold current personal and project licenses from the home office. Using maternal and direct fetal steroid manipulation, using ultrasound guided injection, during pregnancy we have refined an ovine model of PCOS. We have interrogated this model to report fetal antecedents of adult disease and assess the molecular effects of treatment with ovarian diathermy and exogenous steroids on disease progression. We are now expanding these studies to look at androgenic and estrogenic endocrine disruption, neurodevelopmental programming and the effects of exogenous progesterone supplementation in early pregnancy.

Laboratory-based studies on the molecular regulation of tissue and vascular remodelling in human reproductive tissues and cells:

The Human Corpus Luteum: I have had a long interest in tissue and vascular remodelling in the human corpus luteum (CL). The human CL is fundamentally important in the establishment of pregnancy. We however still do not understand how it works at a molecular and cellular level and there are no contraceptive strategies that target CL function. It is also of major generic importance in the understanding of fundamental cellular processes including its tumour-like development, with intense and highly regulated angiogenesis followed by cell death, protection from malignancy and tissue regression without scarring. We have developed a novel system for in vivo manipulation of the CL in women to mimic maternal recognition of pregnancy. We have supplemented this using primary cultures and co-cultures of luteal cells and transient transfection studies in cell lines. Our studies have made an internationally leading contribution to our increased understanding of how the CL of women is regulated.

Quantitation of microvascular density in vivo: My expertise in luteal angiogenesis has been translated into the development of contrast enhance ultrasound for the quantitative assessment of angiogenesis and microvascular volume. These studies involve preclinical models using the corpus luteum of sheep. Using the predictable changes in microvascular volume quantified in serial tissue sections to validate in vivo CEUS data we are developing algorithms to increase the reliability of microvascular volume and flow measurements. The goal of this research is the development of novel low-cost clinical tools for use in monitoring angiogenesis in tumours and cardiac muscle.

Molecular mechanisms underpinning pathology of the reproductive tract: I have also used the tools and ideas developed in the laboratory studies of the CL to investigate the molecular mechanisms involved in important clinical problems involving aberrant tissue and vascular remodelling in the female reproductive tract. These include ovarian cancer and ectopic pregnancy and endometriosis. 

Collaborative Activity

My main collaborators are:

Corpus luteum: A. Prof Junko Nio-Kobayashi (Japan), Dr Xavier Donadeu (Roslin, University of Edinburgh)

Fetal programming of disease: Prof Paul Fowler (University of Aberdeen), Prof Cheryl Ashworth (Roslin, University of Edinburgh)

Polycystic ovary syndrome: Dr Mick Rae (Edinburgh Napier University), Prof Alan McNeilly (University of Edinburgh), Prof Steve Franks (Imperial College)

Contrast enhanced ultrasound: Dr Vasilis Sboros (Heriot Watt University)

Endometriosis and Early pregnancy Problems: Prof Andrew Horne (University of Edinburgh), Prof Arri Coomaraswamy (University of Birmingham)

 

Teaching

I am a passionate teacher and motivator whose direct contribution to undergraduate teaching includes year 1, year 2 and year 4 MBChB, and year 2, year 3 and year 4 BSc(hons). I lecture widely to postgraduates including taught MSc programmes, GPs, trainees and junior doctors preparing for MRCOG and DRCOG examinations.

I am the Module Organiser for Obstetrics and Gynaecology in Year 4 MBChB. I chair the teaching, implementation and assessment committee in Obstetrics and Gynaecology.  I am the co-ordinator of adjustments for MBChB in the College of Medicine and Veterinary Medicine. I have had a major practical and strategic input into postgraduate examination and assessment within the RCOG. This includes working parties on the national undergraduate curriculum, the MRCOG part 1 examination and the new MRCOG examination. I am a past chair of the MRCOG EMQ Committee and currently chair the MRCOG Implementation Committee.

I am a member of the exam boards for year 4 MBChB and BSc(hons) in Reproductive Biology. I have been external examiner for year 5 MBChB at the University of Dundee and currently am external examiner for year 3 MBChB at the University of Liverpool. I have been postgraduatre external examiner in Singapore and Sri Lanka and am currently external examiner for the MFRSH.

 

Research students

I am or have been the supervisor of the postgraduate laboratory research of 9 PhD students and 17 MSc students. In addition I have supervised the research thesis of 18 BSc(hons) students. I have supervised two post-doctoral scientists,  who are both current senior Research Fellows at Russell Group Universities, and a visiting scientist who is setting up a lab to study human luteal cells in Japan.

PhD (1st Supervisor):           

Dr Michelle Myers BSc (2004-2007) In vitro modelling of endocrine and paracrine interactions in the human ovary. Thesis submitted within three years. Next appointment: Post-doctoral researcher, Baylor College of Medicine, Houston, TX, USA.

Dr Kirsten Hogg MSc (2008-2011) Novel approaches to the development and assessment of an ovine model of polycystic ovary syndrome. Thesis submitted within three years. Next appointment: Post-doctoral researcher, University of British Colombia, Vancouver, Canada.

Dr Fiona Connolly MSc (2010-2013) Reproductive and metabolic programming by exogenous steroids. Thesis submitted within three years. Next appointment: Clinical Trial Laboratory Quality Assurance, Edinburgh, UK.

Katarzyna Siemienowicz MSc (2013-date) Causes and consequences of metabolic dysregulation in an ovine model of polycystic ovary syndrome

Education/Academic qualification

Doctor of Medicine, The human corpus luteum: functional and structural effects of maternal recognition of pregnancy, University of Edinburgh

Award Date: 1 Jan 1998

Bachelor of Medicine and Bachelor of Surgery, University of Edinburgh

Award Date: 1 Jan 1990

Bachelor of Science (Honours), An investigation of cell lines transfected with the ras gene in close proximity to an inducible promoter, University of Edinburgh

Award Date: 1 Jan 1988

Keywords

  • RG Gynecology and obstetrics
  • Reproductive Medicine

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