Telephone: 0131 242 2687 Email: W.C.Duncan@ed.ac.uk
Our laboratory-based studies investigate how the ovary works in health and disease. As well as examining crucial pathways responsible for normal fertility we use our research to discover how the ovary can repeatedly remodel and repair itself without problem and how the environment before birth can program lifelong abnormalities of reproductive function.
Although we have other areas of ongoing and collaborative research there are two main areas that we study.
Resilience, Repair and Replacement:
The human corpus luteum is of fundamental importance in the regulation of human fertility. It is a transient gland in the ovary that is formed after the egg is released and lasts for two weeks. It is the most active gland in the body producing huge amounts of the hormone progesterone. It is up to 2cm in diameter and has a blood supply, per unit mass, eight times that of the kidney. That means that during its formation there is an intense and predictable development of new blood vessels. As this process of angiogenesis is hugely important in cancer biology, inflammation and cardiovascular disease by studying how it is regulated in the corpus luteum we get insights that translate to other research disciplines. In the absence of pregnancy the corpus luteum will undergo intense remodelling to lose its blood supply and disappear without scarring. It is this process of luteolysis that causes a woman to have a normal period. If the woman conceives a hormone released from the pregnancy blocks this regression to maintain the structure, function and blood supply of the corpus luteum. It is this that delays the period, supports the pregnancy and allows human fertility. Even although it is so important we don’t understand how it works. We are studying the effects of pregnancy hormone on the ovary to determine how the corpus luteum disappears and how this can be blocked. This also gives us insights into the scarless healing seen in the ovary that has important implications for other body systems and tissue resilience, repair and replacement. Review Publication (PDF).
Living a long and healthy life:
We are studying how reproduction and ovarian structure and function are programmed by alterations in steroids in the fetal environment before birth. Polycystic ovary syndrome is the most common endocrine and reproductive disorder of women. It affects 7-8% of women and is associated with many clinical problems including irregular periods, infertility, hirsuitism, miscarriage, obesity, insulin resistance, fatty liver and diabetes. We know if there is a transient change to the steroid environment before birth we can induce these lifelong problems. We are using a large animal model of PCOS to study how the hormonal, ovarian and metabolic abnormalities are programmed before birth with a view to their early detection and manipulation to promote a long and healthy life. We are able to specifically alter the fetal steroid environment for a short time in pregnancy and investigate how these alterations translate into long-term changes in the reproductive, ovarian and metabolic features of the adult.
Current research projects
- Molecular regulation of the structure and function of the human corpus luteum
- Regulation, effects and manipulation of TGFβ family members and prostaglandins on human ovarian cells
- Regulation and manipulation of the SLIT/ROBO genes in human ovarian cells
- Real-time microbubble imaging of the ovarian microvasculature using ultrasonography
- Biomarkers of tubal ectopic pregnancy
- Characterisation of an ovine model of PCOS
- The effect of maternal and fetal gestational exposure to testosterone on the structure and function of metabolic and reproductive tissues
- The effect of direct fetal gestational exposure to steroids on the structure and function of metabolic and reproductive tissues
- Manipulation of ovarian function in an ovine model of PCOS
- Manipulation of ovine immunotolerance using a prenatal paradigm
£672,767 Dr V. Sboros, Prof A.S. McNeilly, Dr W.C. Duncan, et al., November 2008 (3 years)
Medical Research Council
“The development of contrast enhanced ultrasonography using the sheep ovarian model of microvascular regulation”
£83,131 Dr W.C. Duncan
May 2010 (2 years)
The Cunningham Trust
“Investigation and manipulation of functional interactions between paracrine regulators of human ovarian tissue and vascular remodelling”
£790,411 Dr W.C. Duncan, Dr M.T. Rae, Prof A.S. McNeilly
May 2010 (3 years)
Medical Research Council
“Polycystic ovary syndrome (PCOS): manipulation of hormonal, metabolic and ovarian phenotypes using a developmental model”
£500,000 Dr W.C. Duncan
April 2009 (4 years)
Scottish Funding Council
“Scottish Senior Clinical Fellowship”
Hogg K., Etherington S.L., Young J., McNeilly A.S. Duncan W.C. (2010) Inhibitor of differentiation (Id) genes are expressed in the steroidogenic cells of the ovine ovary and are differentially regulated by members of the transforming growth factor (TGF)-beta family. Endocrinology 151: 1247-1256.
5-year IF 5.1
Dickinson R.E., Stewart A.J, Myers M., Millar R.P., Duncan W.C. (2009). Differential expression and functional cross-talk of luteinizing hormone receptor (LHR) splice variants in human luteal cells: implications for luteolysis. Endocrinology 150: 2873-2881.
5-year IF 5.1
Dickinson R.E., Myers M., Duncan W.C. (2008). Novel regulated expression of the SLIT/ROBO pathway in the ovary: possible role during luteolysis in women. Endocrinology 149: 5024-5034.
5-year IF 5.1
Duncan W.C., van den Driesche S., Fraser H.M. (2008). Inhibition of vascular endothelial growth factor in the primate ovary up-regulates hypoxia-inducible factor-1alpha in the follicle and corpus luteum. Endocrinology 149: 3313-3320.
5-year IF 5.1
Horne A.W., van den Driesche S., King A.E., Burgess S., Myers M., Ludlow H., Lourenco P., Ghazal P., Williams A.R., Critchley H.O., Duncan W.C. (2008). Endometrial inhibin/activin beta-B subunit expression is related to decidualization and is reduced in tubal ectopic pregnancy. J. Clin. Endocrinol. Metab. 93: 2375-2382.
5-year IF 6.46
H index 19
Lyndsey Boswell (Research Technician)
Junko Nio-Kobayashi (Visiting post-doctoral Fellow)
Fiona Connolly (PhD Student)
Kirsten Hogg (PhD) student
Professor A.S. McNeilly (MRC )
Dr M.T. Rae (Napier Edinburgh University)
Dr A.W. Horne (Edinburgh University)
Professor P. Fowler (Aberdeen University)
Dr V. Sboros (Edinburgh University)
Chair RCOG Part II MRCOG extended matching question committee (2008-2012)
RCOG Examination and Assessment Committee (2008-2012)
RCOG Academic Committee (2008-2011)
Translational Research Panel, Health Research Board, Ireland (2007)
Society for Reproduction and Fertility management committee (2005-2008)
Chair – Haematology, oncology, breast disease, renal, urology and obstetrics and gynaecology exam sub-board, University of Edinburgh (2009 – date)
Course Organiser – Obstetrics and Gynaecology (year 4), University of Edinburgh (2000 – date)
External Examiner (Year 5 MBChB) University of Dundee