Professor of Reproductive Medicine, University of Edinburgh
Head, School of Clinical Sciences, University of Edinburgh
Honorary Consultant in Obstetrics and Gynaecology,
Edinburgh Royal Infirmary, NHS Lothian
BSc(Hons), MBChB (Hons), MD, FRCOG, FRANZCOG, FSB, FMedSci, FRSE
Telephone: 0131 242 6858 Email: email@example.com Room: C1.05
Sheila Milne (PA)
Email: Sheila.Milne@ed.ac.uk Room: C1.17
Our research specifically examines local mechanisms within the womb-lining (endometrium) involved in menstruation, implantation and early pregnancy loss. Both menstruation and implantation display features common to inflammatory events. We study the cascade of events that occur in cells of the endometrium that are triggered by withdrawal of the hormone, progesterone (P). This occurs at the end of each monthly cycle prior to a period. As a consequence of P-withdrawal, substances that are mediators of inflammation and populations of immune cells are increased in the endometrium. We are interested in the complex dialogue between circulating steroid hormones and the many different cell types, including immune cells that constitute the endometrium.
We also study factors that switch on production of molecules involved in blood vessel growth and repair in the endometrium; both necessary events to prepare for the next menstrual cycle. If we can understand how the womb heals itself without scarring as women go through their menstrual cycles we hope we will contribute valuable information relevant to inflammation and scarring throughout the body. If these events are disturbed then abnormal menstrual bleeding may be the result. We are therefore studying endometrial samples collected from women attending with menstrual complaints. We hope that information about the molecular and cellular pathways involved in menstruation will help identify new targets for treatment, especially if these treatments could be delivered directly to the uterus.
Study of endocrine/immune regulation of endometrial bleeding in women (physiological and pathological) is complemented by murine models of menstruation/uterine bleeding.
Current research projects:
- Mechanisms involved in menstruation and endometrial repair.
- Novel injury-repair mechanisms: local cortisol metabolism in the female reproductive tract.
- Establishment of murine models of menstruation and uterine bleeding.
- Novel magnetic resonance imaging of vascular and extracellular matrix morphology in women with uterine fibroids.
- Mechanism of action of progesterone receptor modulators (PRMs)
Current Clinical Trials:
Current Grants held as Principal Investigator
- Efficacy and Mechanism Evaluation Programme (12/206/52)
Title: Ulipristal acetate versus conventional management of heavy menstrual bleeding (HMB; including uterine fibroids): a randomised controlled trial and exploration of mechanism of action (UCON trial).
Investigators: Prof HOD Critchley (PI), Dr J Daniels, Prof ARW Williams, , Prof N Roberts,
Dr S Semple, Prof S Battacharya, Dr D Hapangama, Prof M Lumsden, Dr TJ Clark,
Mr LJ Middleton, Dr P Smith, Ms E Nicholls.
- MRC Developmental Clinical Studies
Title: Reversing endometrial glucocorticoid deficiency in heavy menstrual bleeding.
Investigators: Prof HOD Critchley, Prof BR Walker, Dr P Warner, Dr C Weir, Prof JP Iredale, Prof PTK Saunders, Dr S Semple, Prof SG Hillier
Current Grants held as Co-Investigator
- National Institute for Health Research
Title: PRE-EMPT: Preventing recurrence of endometriosis by means of long acting progestogen therapy. Investigators: Prof S Battacharya (PI, Aberdeen), Dr J Daniels (PI, Birmingham), T Roberts (Birmingham), A Horne (Edinburgh), Prof J Gupta (Birmingham),
Mr TJ Clark (Birmingham), Dr C Becker (Oxford), Dr G Jones (Sheffield), Prof E Denny (Birmingham City), Dr K Cooper (NHS Grampian), Prof HOD Critchley (Edinburgh),
Mr L Middleton (Birmingham), Dr C Whittall (RJAH, Oswestry), Dr A Prentice (Cambridge),
Dr E Saridogan (UCL)
- Grant body: MRC Centre Grant
Title: Establishment of MRC/University of Edinburgh Centre for Reproductive Health Investigators: Prof PTK Saunders (PI), Prof HOD Critchley (Co-I), Prof JE Norman (Co-I),
Prof RA Anderson (Co-I)
Recent Grants held as Principal Investigator:
- TENOVUS SCOTLAND The Women of Scotland Luncheon “Women’s Health” Award
Title: A new era in the treatment of chronic debilitating women’s health disorders using selective progesterone receptor modulators (PRMs).
Investigators: Prof HOD Critchley, Prof PTK Saunders, Dr ARW Williams
- Grant body: The Wellcome Trust (083908/Z/07/Z)
Title: The role of androgens in endometrial proliferation and differentiation.
Investigators: HOD Critchley, PTK Saunders
- Grant body: Translational Medicine Research Collaboration (WHMSB-EU-131)
Title: Novel magnetic resonance imaging strategies as a non-invasive biomarker of vascular and extracellular matrix morphology in women with uterine fibroids.
Investigators: HOD Critchley, D Newby, J Walker, G McKillop, M Bastin, I Marshall, A Williams,
A Horne, R Millar, R Anderson
Recent Grants held as Co-Investigator
- Grant body: MRC Project Grant (G0900550)
Title: Postovulatory ovarian repair: a role for LOX in scar-free adult healing.
Investigators: SG Hillier, HOD Critchley, JI Mason, JP Iredale, S Brown, CR Harlow
- Sassarini J, Lumsden MA, Critchley HO (2015) Sex hormone replacement in ovarian failure – New treatment concepts. Best Pract Res Clin Endocrinol Metab 29:105-114 PMID 25617176
- Warner P, Weir CJ, Hansen CH, Douglas A, Madhra M, Hillier SG, Saunders PT, Iredale JP, Semple S, Walker BR, Critchley HO Low dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM). BMJ Open 5:e006837 doi:10.1136/bmjopen-2014-006837 PMID 25588784
- Thrippleton MJ, Munro KI, McKillop G, Newby DE, Marshall I, Roberts N, Critchley HO (2015) Unbiased and Efficient Estimation of the Volume of the Fibroid Uterus Using the Cavalieri Method and Magnetic Resonance Imaging. Reprod Sci 22: 15-22 PMID 25332217
- Munro, KI, Thrippleton MJ, Williams AR, McKillop G, Walker J, Horne AW, Newby DE, Anderson RA, Semple SI, Marshall I, Lewis SC, Millar RP, Bastin ME, Critchley HO (2014) Quantitative Serial MRI of the Treated Fibroid Uterus. PLoS ONE 9:e89809 PMID 24608161
- Cousins FL, Murray A, Esnal A, Gibson DA, Critchley HO, Saunders PT (2014) Evidence from a Mouse Model that Epithelial Cell Migration and Mesenchymal-Epithelial Transition Contribute to Rapid Restoration of Uterine Tissue Integrity during Menstruation. PLoS ONE 9: e86378 PMID 24466063
- Gibson DA, McInnes KJ, Critchley HO, Saunders PT (2013) Endometrial Intracrinology – Generation of an Estrogen-dominated Microenvironment in the Secretory Phase of Women.
J Clin Endocrinol Metab 98: E1802-E1806 PMID 24014622
- Wilkens J, Male, V, Ghazal, P, Forster T, Gibson D, Williams AR. Brito Mutunayagam SL, Craigon M, Lourenco P, Cameron IT, Chwalisz K, Moffett A, Critchley HO. (2013) Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil. J Immunol 191:2226-2235 PMID 23913972
- Thiruchelvam U, Dransfield I, Saunders PT, Critchley HO. (2013) The importance of the macrophage within the human endometrium. J Leukoc Biol 93:217-225 PMID 23108100
- O’Donnell R, Warner P, Lee RJ, Walker J, Bath LE, Kelnar CJ, Wallace WH, Critchley HO (2012) Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Hum Reprod 27:1130-1138 PMID 22343553
- Maybin JA, Barcroft J, Thiruchelvam U, Hirani N, Jabbour HN, Critchley HO (2012) The presence and regulation of connective tissue growth factor in the human endometrium.
Hum Reprod 27:1112-1121 PMID 22328559
- Critchley HO, Maybin JA (2011) Molecular and cellular causes of abnormal uterine bleeding of endometrial origin. Semin Reprod Med 29:400-409 PMID 22065326
- Thrippleton MJ, Bastin ME, Munro KI, Williams AR, Oniscu A, Jansen MA, Merrifield GD, McKillop G, Newby DE, Semple SI, Marshall I, Critchley HO (2011) Ex vivo water diffusion tensor properties of the fibroid uterus at 7 T and their relation to tissue morphology. J Magn Reson Imaging 34:1445-1451 PMID 21953730
- Marshall E, Lowrey J, MacPherson S, Maybin JA, Collins F, Critchley HO, Saunders PT (2011) In Silico Analysis Identifies a Novel Role for Androgens in the Regulation of Human Endometrial Apoptosis. J Clin Endocrinol Metab 96:E1746-1755 PMID 21865353
- Cervello I, Mas, A, Gil-Sanchis C, Peris L, Faus A, Saunders PT, Critchley HO, Simon C (2011) Reconstruction of Endometrium from Human Endometrial Side Population Cell Lines. PLoS One 6: e21221 PMID 21712999
- Maybin JA, Hirani N, Brown P, Jabbour HN, Critchley HO (2011) The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair. J Clin Endocrinol Metab 96: 2475-2483 PMID 21677035
- Maybin JA, Battersby S, Hirani N, Nikitenko LL, Critchley HO, Jabbour HN (2011)
The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair. Endocrinology 152: 2845-2856 PMID 21558311
- Maybin JA, Critchley HO (2011) Progesterone: a pivotal hormone at menstruation. Ann N Y Acad Sci 1221: 88-97 PMID 21401635
- Maybin JA, Hirani N, Jabbour HN, Critchley HO (2011) Novel Roles for Hypoxia and Prostaglandin E2 in the Regulation of IL-8 During Endometrial Repair. Am J Pathol 178: 1245-1256 PMID 21356375
- Munro MG, Critchley HO, Broder MS, Fraser IS; for the FIGO Working Group on Menstrual Disorders (2011) FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynecol Obstet 113: 3-13 PMID 21345435
- Warner P, Guttinger A, Glasier AF, Lee RJ, Nickerson S, Brenner RM, Critchley HO (2010) Randomized placebo-controlled trial of CDB-2914 in users of levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding. Hum Reprod 25: 345-353 PMID 19897857
- Kane, N, Kelly R, Saunders PT, Critchley HO. (2009) Proliferation of uterine natural killer cells is induced by hCG and mediated via the mannose receptor. Endocrinology 150: 2882-2888. PMID 19196802
- Rae M, Mohamad A, Price D, Hadoke PWF, Walker BR, Mason JI, Hillier SG, Critchley HO. (2009) Cortisol in activation by 11βHSD2 may enhance endometrial angiogenesis via reduced thrombospondin-1 in heavy menstruation. J Clin Endocrinol Metab 94:1443–1450. PMID 19158196
- Maybin JA, Critchley HO (2015) Menstrual physiology: implications for endometrial pathology and beyond. Hum Reprod Update doi:10.1093/humupd/dmv038 [epub ahead of print]
Sheila Milne (PA)
Bianca de Leo
Professor Philippa Saunders
Professor John Iredale
Professor Brian Walker
Professor Stephen Hillier
Professor Andrew Horne
Professor Neil Roberts
Dr Ailsa Gebbie
Dr Pamela Warner
Dr Chris Weir
Dr Scott Semple
Dr Nik Hirani
Professor Mary Ann Lumsden (Glasgow)
Professor Ashley Moffett (Cambridge)
Professor Siladitya Bhattacharya (Aberdeen)
Dr Justin Clark (Birmingham)
Dr Dharani Hapangama (Liverpool)
Professor Peter Rogers (Melbourne, Australia)
Professor Martha Hickey (Melbourne, Australia)
Professor Ian Fraser (Sydney, Australia)
Professor Mac Munro (Los Angeles, USA)
Dr Ov Slayden (Portland, USA)
Professor Carlos Simon (Valencia, Spain)
Professor Felice Petraglia (Siena, Italy)
- Centre for Trophoblast Research (CTR) – Member of CTR Scientific Advisory Board (2014-2018)
- Royal Society of Edinburgh – Member of RSE/Caledonian Research Foundation Fellowship Award Committee (from 2013)
- Academy of Medical Sciences – Member Selection Panel for Academy’s Starter Grants for Clinical Lecturers Scheme (2013-2016)
- Co-Chair of Reproductive Health Expert Advisory Group, Scottish Government (from 2014)
- International Federation of Gynecology and Obstetrics (FIGO) Menstrual disorders Working Group – Co-Chair and Founding Member
- President of Edinburgh Obstetrical Society (from 2014)
- European Society of Human Reproduction and Embryology (ESHRE): Past Coordinator ESHRE Special Interest Group Endometriosis & Endometrium (SIGEE) (2012-2015) (Coordinator 2009-2012)
- Board Member World Endometriosis Society (2011-2015)
- Society for Gynecologic Investigation (SGI) – Member of Council (2010-2013)
- National Reproductive Health Research Network Menstrual Disorders Clinical Study Group – Member of Executive Board (from 2011)
- Journal of Reproductive Immunology
- Reproductive Sciences
- Journal of Endometriosis
- F1000 Research
- PLOS ONE
- Human Reproduction Update