Our research has two main areas: 1) discovering how the ovary supports early pregnancy and 2) understanding polycystic ovary syndrome (PCOS), and its hormonal and metabolic imbalances, and finding new treatment targets. Professor Colin Duncan Professor of Reproductive Medicine and Science Contact details Email: W.C.Duncan@ed.ac.uk Research Interests 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 and metabolic function. 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 to support early pregnancy. 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. We are also looking at the effects of progesterone and its supplementation during pregnancy. 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 use 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. Key projects Mechanisms for manipulating of LH signalling in human steroidogenic cells The effect of maternal and fetal gestational exposure to testosterone on the structure and function of metabolic and reproductive tissues Adipose tissue structure and function in PCOS Development and treatment of obesity associated with PCOS Publications Development of an acute ovine model of polycystic ovaries to assess the effect of ovarian denervation. Duncan WC, Nicol LM, O'Hare R, Witherington J, Miranda JA, Campbell BK, Thomas JL, Rae MT. Front Endocrinol (Lausanne). 2023 Oct 24;14:1285269. doi: 10.3389/fendo.2023.1285269. eCollection 2023. PMID: 37941906 Free PMC article. Hepatic Mitochondrial Dysfunction and Risk of Liver Disease in an Ovine Model of "PCOS Males". Siemienowicz KJ, Filis P, Thomas J, Fowler PA, Duncan WC, Rae MT. Biomedicines. 2022 May 31;10(6):1291. doi: 10.3390/biomedicines10061291. PMID: 35740312 Free PMC article. Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial. Horne AW, Tong S, Moakes CA, Middleton LJ, Duncan WC, Mol BW, Whitaker LHR, Jurkovic D, Coomarasamy A, Nunes N, Holland T, Clarke F, Doust AM, Daniels JP; GEM3 collaborative. Lancet. 2023 Feb 25;401(10377):655-663. doi: 10.1016/S0140-6736(22)02478-3. Epub 2023 Feb 1. PMID: 36738759 Clinical Trial. Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome. Siemienowicz KJ, Furmanska K, Filis P, Talia C, Thomas J, Fowler PA, Rae MT, Duncan WC. Mol Cell Endocrinol. 2021 Apr 5;525:111196. doi: 10.1016/j.mce.2021.111196. Epub 2021 Feb 6. PMID: 33556473 Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses. Siemienowicz KJ, Wang Y, Marečková M, Nio-Kobayashi J, Fowler PA, Rae MT, Duncan WC. Sci Rep. 2020 Dec 14;10(1):21920. doi: 10.1038/s41598-020-78976-x. PMID: 33318609 Free PMC article. Aberrant subcutaneous adipogenesis precedes adult metabolic dysfunction in an ovine model of polycystic ovary syndrome (PCOS). Siemienowicz KJ, Coukan F, Franks S, Rae MT, Duncan WC. Mol Cell Endocrinol. 2021 Jan 1;519:111042. doi: 10.1016/j.mce.2020.111042. Epub 2020 Oct 1. PMID: 33010309 Insights into Manipulating Postprandial Energy Expenditure to Manage Weight Gain in Polycystic Ovary Syndrome. Siemienowicz K, Rae MT, Howells F, Anderson C, Nicol LM, Franks S, Duncan WC. iScience. 2020 Jun 26;23(6):101164. doi: 10.1016/j.isci.2020.101164. Epub 2020 May 15. PMID: 32464593 Free PMC article. Fetal androgen exposure is a determinant of adult male metabolic health. Siemienowicz KJ, Filis P, Shaw S, Douglas A, Thomas J, Mulroy S, Howie F, Fowler PA, Duncan WC, Rae MT. Sci Rep. 2019 Dec 27;9(1):20195. doi: 10.1038/s41598-019-56790-4. PMID: 31882954 Free PMC article. Urinary estrogens as a non-invasive biomarker of viable pregnancy in the giant panda (Ailuropoda melanoleuca). Wilson KS, Wauters J, Valentine I, McNeilly A, Girling S, Li R, Li D, Zhang H, Rae MT, Howie F, Andrew R, Duncan WC. Sci Rep. 2019 Sep 4;9(1):12772. doi: 10.1038/s41598-019-49288-6. PMID: 31484972 Free PMC article. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, Eapen AK, Roberts T, Ogwulu CC, Goranitis I, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Kriedt K, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingam N, Watkins L, Wykes C, Horne A, Jurkovic D. N Engl J Med. 2019 May 9;380(19):1815-1824. doi: 10.1056/NEJMoa1813730. PMID: 31067371 Clinical Trial. Group Members Yuan Wang (PhD student) Riada McCredie (MD student) Media and engagement Thanks to Alice Haskell who we worked with to create this animation. Principal collaborators Professor A.S. McNeilly (Emeritus, Edinburgh University) Professor S. Franks (Imperial College) Professor M.T. Rae (Edinburgh Napier University) Professor A.W. Horne (Edinburgh University) Professor P. Fowler (Aberdeen University) Professor HM Picton (University of Leeds) Professor E.E. Telfer (Edinburgh University) Dr V. Sboros (Heriot Watt University) Dr J. Nio-Kobayashi (Hokkaido University) Dr K. Siemienowicz (Edinburgh Napier University) Funders Medical Research Council Society for Reproduction and Fertility HTML This article was published on 2024-09-10
