Professor Hilary O D Critchley

Hilary CritchleyJob Title:
Professor of Reproductive Medicine/Honorary Consultant in Obstetrics and Gynaecology
University of Edinburgh
Head, School of Clinical Sciences.

Contact details:
Telephone: 0131 242 6858
Email: hilary.critchley@ed.ac.uk

Sheila Milne (PA)
Email: Sheila.Milne@ed.ac.uk

Research Interests

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.

Current research projects:

  • Mechanisms involved in menstruation and endometrial repair.
  • Novel injury-repair mechanisms: local cortisol metabolism in the female reproductive tract.
  • To establish murine models to study menstruation.
  • The role of androgens in endometrial proliferation and differentiation.
  • Postovulatory ovarian repair: a role for LOX in scar-free adult healing. (co-investigator)
  • Novel magnetic resonance imaging of vascular and extracellular matrix morphology in women with uterine fibroids.
  • Mechanisms of chlamydial infection, tissue inflammation and scarring. Effects of chlamydial infection on Fallopian tube biology (with Dr Andrew Horne, Professors John Iredale and
    Sarah Howie; and Professor Gary Entrican at Moredun Research Institute, Edinburgh).

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Grants:

  • 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
  • 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
  • Grant body: Bayer Schering Pharma AG
    Title: To establish and validate a human endometrial xenograft model to study menstruation.
    Investigators: Prof HOD Critchley
  • 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
  • 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
  • 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)

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Selected publications

  1. 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 PMID 23913972 [Epub ahead of print]
  2. 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
  3. 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
  4. 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
  5. Critchley HO, Maybin JA (2011) Molecular and cellular causes of abnormal uterine bleeding of endometrial origin.  Semin Reprod Med 29:400-409 PMID 22065326
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Maybin JA, Critchley HO (2011) Progesterone: a pivotal hormone at menstruation.  Ann N Y Acad Sci 1221: 88-97 PMID 21401635
  12. 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
  13. 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
  14. Horne AW, Shaw JL, Murdoch A, McDonald SE, Williams AR, Jabbour HN, Duncan WC, Critchley HO (2011) Placental Growth Factor: A Promising Diagnostic Biomarker for Tubal Ectopic Pregnancy.  J Clin Endocrinol Metab 96: E104-108 PMID 21047920
  15. Kane NM, Jones M, Brosens JJ, Kelly RW, Saunders PT, Critchley HO (2010)  TGFβ1 Attenuates Expression of Prolactin and IGFBP-1 in Decidualized Endometrial Stromal Cells by both SMAD-Dependent and SMAD-Independent Pathways.  PLOS One 5:e12970. PMID 20885978
  16. 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
  17. Horne AW, King AE, Shaw E, McDonald SE, Williams ARW, Saunders PT, Critchley HO (2009)  Attenuated Sex Steroid Receptor Expression in Fallopian Tube of Women with Ectopic Pregnancy.  J Clin Endocrinol Metab 94: 5146-5154. PMID 19864448
  18. King AE, Horne AW, Hombach-Klonisch S, Mason JI, Critchley HO. (2009) Differential expression and regulation of nuclear oligomerization domain proteins NOD1 and NOD2 in human endometrium: a potential role in innate immune protection and menstruation. Mol Hum Reprod 15: 311-319. PMID 19273470
  19. 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
  20. 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

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Staff/group members

Alison Murray
Jacqueline Maybin
Catherine Murray
Sheila Milne (PA)
Moira Nicol

PhD/MD Students

Greg Armstrong
Serge Madhra
Paula Lourenco
Uma Thirulchelvam

Principal collaborators

Local
Professor Philippa Saunders
Professor John Iredale
Professor Brian Walker
Professor Stephen Hillier
Dr Chris Harlow
Dr Ailsa Gebbie
Dr Pamela Warner
Professor Sarah Howie
Professor Gary Entrican
Dr Nik Hirani

National
Professor Mary Ann Lumsden (Glasgow)
Professor Ashley Moffett (Cambridge)

International
Professor Peter Rogers (Australia)
Professor Martha Hickey (Australia)
Professor SK Dey (USA)
Dr Ov Slayden (USA)
Professor Carlos Simon (Spain)
Professor Felice Petraglia (Italy)

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Responsibilities

  • Society for Gynecologic Investigation (SGI) – Member of Council (from March 2010)
  • European Society of Human Reproduction and Embryology (ESHRE):
  • Past Coordinator ESHRE Special Interest Group Endometriosis & Endometrium (SIGEE) (Coordinator 2009-2012)
  • Member of ESHRE International Scientific Committee 2010 (Rome), 2011 (Stockholm),
    2012 (Istanbul)
  • Royal College of Obstetricians and Gynaecologists: Member of RCOG Academic Committee 2009-present
  • Board Member World Endometriosis Society

Other Committee membership

  • Chair – Reproductive Health Advisory Group (RHAG) NHS Quality Improvement Scotland
  • Lead for Women’s Health (Edinburgh), Scottish Academic Health Sciences Collaboration
    (from September 2009)
  • Member of Council – Society of Gynaecologic Investigation (2010-2013)
  • Chair – Sectional Committee 5, Academy of Medical Sciences
  • Member of Council – Scottish Society for Experimental Medicine
  • Junior Vice President (from October 2010) – Edinburgh Obstetrical Society

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Current Editorial Board Membership

  • Journal of Reproductive Immunology
  • Reproductive Sciences
  • Journal of Endometriosis
  • F1000 Research
  • PLOS ONE
  • Human Reproduction Update

Previous Editorial Board Membership

  • Molecular Human Reproduction (2008-2011)
  • Journal of Endocrinology (from 2001-2008)
  • Journal of Clinical Endocrinology and Metabolism (2004-2007)
  • Reproduction (2002–2007)
  • Reviews of Reproduction (1999-2000)
  • Clinical Endocrinology (1997-2000)

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