Professor Paul Fowler

  Professor Paul Fowler The University of Aberdeen School of Medicine & Dentistry Professor Paul Fowler Chair in Translational Medical Sciences work +44 (0)1224 437528 work fax +44 (0) 1224 437465 pref

Institute of Medical Sciences Division of Applied Medicine University of Aberdeen Foresterhill Aberdeen AB25 2ZD Scotland

Chair in Translational Medical Sciences

BSc (Hons 1st) Zoology, Aberdeen 1982. PhD, Aberdeen 1986, FSB

Professor Paul Fowler

Contact Details

Telephone: +44 (0)1224 437528
Fax: +44 (0) 1224 437465
Email:

p.a.fowler@abdn.ac.uk

Address:

Institute of Medical Sciences Division of Applied Medicine University of Aberdeen Foresterhill Aberdeen AB25 2ZD Scotland

hCard

I am a signatory of the The 2013 Berlaymont Declaration on Endocrine Disrupters.

European Commission: Science in Society - How gender analysis contributes to research - REEF Project as a case study in Gendered Innovations:

Thanks to for awarding a summer studentship:

"Proteomic analysis of the effects of maternal smoking on the second trimester human fetal gonad "

 

Professional Society Membership:

         

     

I am a long-term member of Fauna & Flora International 


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Biography

Professor Fowler received his BSc Hons and PhD in Zoology at the University of Aberdeen. He later moved to Obstetrics & Gynaecology, University of Aberdeen, to work on ovarian hormones and antiprogesterones.  In 2000 he moved to the Institute of Medical Sciences, University of Aberdeen as a Professor of Translational Medical Sciences and is currently lead for the Cell, Developmental & Cancer Biology Research programme at Aberdeen.

Professor Fowler has spent much of his career working on elucidating mechanisms in the regulation of reproduction and has over 100 peer-reviewed publications, book chapters and editorials. At each stage he has made contributions in the use of technologies to answer reproductive questions, including: remote telemetry of body-testis temperature differentials, MRI analysis of body composition and mammary gland, phage library and protein purification techniques to investigate reproductive proteins and proteomic and microarray techniques to study fetal development and endometriosis. Since the turn of the century, his research has focused on the effects of environmental exposures and endocrine disruption on fetal development and subsequent health in both human and animal models. His group is one of the few to work on the normal second trimester human fetus and uses maternal smoking as a model to understand how adverse in-utero environment disturbs fetal development in our own species.



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Research Interests

Since the breakthrough epidemiological studies of the 1980s it has been clear that adult human health is dependent upon fetal development and fetal programming (‘early life programming’). Fetal growth restriction, for example, can lead to hypertension, type 2 diabetes, obesity and cardiovascular disease in the adult. Dysfunctional changes in the fetus can arise through other mechanisms, such as maternal cigarette smoking or environmental pollutant exposure and the health trajectory of an individual is likely to depend upon the pollutant burden carried at birth. Fetal pollutant exposure has clear adverse effects on development but we currently have very little knowledge about levels of fetal exposure to “real-life” complex pollutant cocktails and developmental consequences. This fundamental lack of knowledge is a major impasse to developing strategies for reducing fetal pollutant burdens and predicting likely health outcomes. Available data is limited, and often indirect (i.e. animal models or surrogates of exposure), but all studies suggest that fetal pollutant exposure affects lifelong health outcomes and, thereby, impacts on the general economy.  

Fetal reproductive development and the environment

(a) Human fetal development and its disruption

Better understanding of events during key stages in reproductive development in the human are key to determining the risks posed by exogenous chemicals, diet and lifestyle on reproductive health in humans, from breast cancer to infertility, testicular cancer to endometriosis, sperm counts to developmental defects. This kind of data is also key to translating the applicability and importance of findings in animal models to the human. Cigarette smoke contains well over 4,000 pollutant chemicals, including potentially toxic elements (PTEs, e.g. cadmium) persistent organic pollutants (POPs, e.g. dioxin) and, of course, nicotine. Many of these chemicals are endocrine-disrupting compounds (EDCs, e.g. nicotine reduces steroidogenesis). Thus, cigarette smoking provides a unique “real-life” model to study endocrine disruption in humans. Since up to 30% of women are smokers and few give up the habit, even when pregnant, it remains a major health challenge. Furthermore, fetal exposure to cigarette smoke chemicals constitutes one of the few models we can use to determine what effects environmental chemicals might have on our own species. This is one of the major models used in my research.

(i) Characterising normal events during human fetal development.

1st gene array study of the human fetal gonad : Gene expression analysis of human fetal ovarian primordial follicle formation. Fowler PA, Flannigan S, Mathers A, Gillanders K, Lea RG, Wood MJ, Maheshwari A, Bhattacharya S, Collie-Duguid ES, Baker PJ, Monteiro A, O'Shaughnessy PJ. J Clin Endocrinol Metab. 2009 Apr;94(4):1427-35.

(ii) Investigating how these events are affected by exposure to cigarette smoke chemicals.

1st  fetal testis gene reduced by maternal cigarette smoking: Maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development. Fowler PA, Cassie S, Rhind SM, Brewer MJ, Collinson JM, Lea RG, Baker PJ, Bhattacharya S, O'Shaughnessy PJ. J Clin Endocrinol Metab. 2008 Feb;93(2):619-26.

(b) Effects of environmental chemicals: using animal models to understand risks

Domestic animals, like humans and all other animals, are exposed to environmental pollutants through exposure to contaminated food, water, air and soil. Environmental pollutants include a range of (mainly) anthropogenic chemicals which have the capacity to interfere, subtly, with hormonal systems and therefore with their capacity to reproduce, rear offspring and fight disease); these chemicals, which included heavy metals and organic compounds of many different classes are described as endocrine disrupting compounds (EDCs). The physiological insult associated with exposure to EDCs involves many different chemical types, each acting on different physiological systems. Furthermore, while environmental concentrations of most individual chemicals are very low and below the No Observable Effect Level (NOEL), in many cases they can act additively to induce a physiological change, even when concentrations of individual chemicals appear harmless.

Empirical evidence in support of this has been provided by our previous work involving exposure of sheep to low (environmental) levels of EDCs through grazing pastures fertilised with sewage sludge (contains high concentrations of multiple EDCs). This work has shown that maternal exposure to sewage sludge treated pasture was associated with perturbation of the fetal hypothalamus-pituitary and ovary, despite the fact that fetal and adult tissue concentrations of individual EDCs at the time of slaughter were minimally increased by such exposure and were at concentrations below the NOEL. Work funded by the Wellcome Trust and the European Union is addressing the effects of exposure during specific windows of time, before and during gestation, on patterns of tissue accumulation and associated physiological changes. 


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Current Research

Current Team: Dr Pan Filis, Ms Samantha Flannigan, Ms Margaret Fraser.

RECENT HUMAN FETAL PUBLICATION  In utero exposure to cigarette smoke dysregulates human fetal ovarian developmental signalling. Fowler PA, Childs AJ, Courant F, MacKenzie A, Rhind SM, Antignac JP, Le Bizec B, Filis P, Evans F, Flannigan S, Maheshwari A, Bhattacharya S, Monteiro A, Anderson RA, O'Shaughnessy PJ. Hum Reprod. 2014 May 20. pii: deu117. [Epub ahead of print]

RECENT ANIMAL MODEL PUBLICATION   Exposure to chemical cocktails before or after conception--- the effect of timing on ovarian development. Bellingham M, Amezaga MR, Mandon-Pepin B, Speers CJ, Kyle CE, Evans NP, Sharpe RM, Cotinot C, Rhind SM, Fowler PA. Mol Cell Endocrinol. 2013 Aug 25;376(1-2):156-72.

PREVIOUS HIGHLIGHT   


Recent plenary and invited presentations:

  • Regulation and dysregulation of primordial follicle formation and activation. 3rd World Congress of Reproductive Biology, 2-4 September 2014, Edinburgh, UK.
  • Environmental chemicals and fetal development. 2ieme Journee des Jeunes Chercheurs de L’IRSET, February 4th 2014, University of Rennes, France.
  • On women and sheep: making and breaking the fetal ovary. INRA, 13 December 2013, Jouy-en-Josas, France.
  • The evidence for EDC involvement in reproductive dysfunction in women. International Workshop: Endocrine Disrupting Chemicals and Female Reproduction. 5-6 November 2013, Uppsala, Sweden.
  • Environment and endocrine disruptors in fetal reproductive development.  IfLS Conference: Reproductive Biology – from gametes to systems, and between generations. 17 September 2013, Southampton, UK.
  • Effects of chemicals on reproductive development. Subspecialist Trainees in Reproductive Medicine and Surgery (STIRMAS). 27 September 2013, Cambridge, UK.
  • Human fetal reproductive development and endocrinology: effects of maternal smoking. 7th Copenhagen Workshop of Endocrine Disrupters, 28-31 May 2013, Copenhagen, Denmark.
  • Impact of endocrine-disrupting compounds (EDCs) on female reproductive health. Fertility 2013, Liverpool, January 3-5 2013.
  • Effects of exposure to environmental chemicals during pregnancy on the development of the male and female reproductive access“. 17th International Congress on Animal Reproduction (ICAR 29012) in Vancouver, British Columbia, Canada, July 29 – August 2, 2012.
  • Environmental exposure in reproductive development and function of the female. World Congress on Reproductive Biology, Cairns Australia 9-11 October 2011.
  • Environmental effects on fetal reproductive development. Australia Society of Reproductive Biology, Cairns Australia 7-9 October 2011.
  • Effects of EDCs on the human foetus: lessons from smoking. 6th Copenhagen Workshop of Endocrine Disrupters, 25-30 April 2011, Copenhagen, Denmark.
  • Maternal smoking and sewage sludge: consequences for fetal gonadal development. Centre for Reproductive Biology Special Symposium: “Endocrine disruptors and reproductive health: separating fact from fiction.” 7 March 2011, University of Edinburgh.
  • Mixtures of environmental chemicals: concentrations and effects in the fetus. Covance Environmental Risk Assessment (ERA) Symposium, 2-3 March 2011, Brussels.
  • In-utero exposures to environmental chemicals and consequences for ovarian development. Gordon Research Conference: “Environmental Endocrine Disrupters", 30 May-4 June 2010, Les Diablerets, Switzerland.
  • Environmental endocrine disruption of the ovary. 37th Nordic Congress of Obstetrics & Gynecology, 15-18 June 2010, Copenhagen, Denmark.
  • Endocrine disruptors and gonadal development.  Symposium: Environmental factors and nosology of the endocrine system, 2-4 October 2009, Athens, Greece.
  • In-utero exposure to environmental chemicals and consequences ovarian development. 5th Copenhagen Workshop of Endocrine Disrupters, 20-22 May 2009, Copenhagen, Denmark.
  • The fetal ovary as a target for disruption. Danish Society of Obstetrics & Gynaecology, 17 April 2009, Copenhagen, Denmark
  • Is the fetus under chemical attack? St George’s University London, 26 March 2009.
  • Gender bending chemicals and the mammalian fetal gonad. XXth International Congress of Zoology, Paris 26-29 August 2008.

Some press releases:



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Collaborations

  • Grateful thanks to Dr Stewart Rhind (James Hutton Institute, Aberdeen, Scotland) for the years of friendship and collaboration before his untimely death.


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Research Grants

  • Fowler PA, Douglas A, Hay D, Iredale J, Fairley S, O'Shaughnessy PJ, Huestis M, The human fetal liver: development and response to maternal drug use. MRC, £588,601.
  • Fowler PA, Filis P, O'Shaughnessy PJ, Does exposure to a complex cocktail of environmental chemicals during pregnancy and lactation alter metabolic and steroid hormone systems in the adult liver? Society for Reproduction & Fertility, Academic Schorlarship, £8,900
  • Bellingham M, Fowler PA, O'Shaughnessy PJ, Prenatal programming of adult disease by maternal smoking: the adrenal gland as a key player? Wellcome Trust Institutional Strategic Support Fund (Catalyst), £18,230.
  • Fowler PA, Bhattacharya S, O'Shaughnessy PJ, Gatekeepers to the cell: which ones operate customs posts in the fetal liver and does maternal smoking allow drugs to slip through? NHS Grampian Endowments, £9,356.
  • Fowler PA, Collinson JM, O’Shaughnessy PJ, Bioincubator system to model toxic effects on the human fetal testis, Chief Scientist Office, £62,078.
  • Fowler PA, Harkany T, O’Shaughnessy PJ, Fetal human gonadal cannabinoid receptors: expression and effects of maternal smoking., NHS Grampian Endowments, £6,713.
  • Fowler PA, Cotinot C, O’Shaughnessy PJ, Inter-species comparison of the onset ovarian follicle formation, Wellcome Trust summer studentship, £5,760
  • Fowler PA, Cotinot C, Fischer B, Lea RG, Pocar P, Sinclair K, Rhind SM, Reproductive effects of environmental chemicals in females (REEF), European Commission, Framework 7, £2,322,380. REEF
  • Fowler PA, Bhattacharya S, Rhind SM, O'Shaughnessy PJ, Does maternal smoking disrupt key developmental sex steroid hormones in the fetus? NHS Grampian Endowments, £10,834.
  • Fowler PA, Sharpe R, Cotinot C, Evans N, Rhind S, Effect of in-utero exposure to environmental chemicals via maternal pasture ingestion on fetal development., Wellcome Trust, £425,786.
  • Fowler PA, Maheshwari A, Bhattacharya S, Follicular assembly in the human fetal ovary, IMS Microarray Core Facility grant, UoA, £6,000.
  • Fowler PA, Wood M, Human fetal gonad: 2 summer research studentships, SRF, £2,640.
  • Skaare JU et al, including Fowler PA, The mechanisms behind toxic effects of POPS, NFR, £170,377.
  • Fowler PA, Bhattacharya S, Hamilton MPR, al-Gubory K, Identification of implantation-related proteins, NHS R&D, £18,500.
  • Fowler PA, Bhattacharya S, Cash P, Circulating biomarkers for endometriosis, University of Aberdeen Commercialisation Fund, £19,095.
  • Shanbhag S, Cruickshank M, Millier I, Murray G, Fowler PA, Molecular basis of granulosa cell tumours, NHS Grampian Endowments, £11,343.
  • Fowler PA, Bhattacharya S, Cash P, Establishing a relationship between endometrial proteins and endometriosis., CSO, £18,856.
  • Fowler PA, Bhattacharya S, Optimisation of an in-vitro model to investigate the human fetal testis, CSO, £15,571.
  • Huhtaniemi I, Fowler PA, Cash P, Charlton H, Novel biological actions of luteinizing hormone and its receptor, Wellcome Trust, £1,408,031.
  • Fowler PA and colleagues, Translational medicine funding: >£700,000.


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Teaching Responsibilities

  • BM4004: Advanced Molecules, membranes and cells
  • BM3803: Epithelial physiology
  • DB3502: Reproductive biology - I coordinate this third year course.
  • SX3003: 6th Century course: An appetite for food and health
  • Phase I MBChB, ME1504: Endocrine and reproductive system


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External Responsibilities

  • Member, Food ingredients and packaging (CEF) panel, EFSA, 2014-2017
  • Member, Editorial Board of the journal Endocrinology, 2014
  • 2009-2013: Chair, Society for Reproduction & Fertility
  • I have served/am serving on committees and council for the Society for Reproduction & Fertility and the British Fertility Society.
  • I am presently on the Editorial Boards/Advisory Boards for the journals Teratology Studies, Reproductive Biology & Endocrinology and Current Medicinal Chemistry.
  • I am/have been an External Examiner for the Universities of Edinburgh and Nottingham and St George's Hospital Medical School, London.
  • Member, AERES research institute evaluation committee, 2013
  • Member, Expert review Panel for CRACK IT NC3Rs, 2012
  • Member, Expert Working Group on BPA, EFSA 2012-2014
  • Member, Gendered Innovations, FP7 case study panel, 2012
  • Member, Standing Evaluation Panel, Environmental Pollution, Swedish Research Council Formas, 2010


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Admin Responsibilities

  • Lead, Cell, Developmental & Cancer Biology Research Programme, 2011-
  • Member, European Advisory Committee
  • Member, Division of Applied Medicine Executive
  • Member, Schools of Medicine & Dentistry and Medical Sciences Joint Research Committee
  • Member, Athena Swann CLSM assessment team


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Other

I work to foster research at Aberdeen via my responsibility for the management, monitoring and generic training of laboratory postgraduate researchers in the School of Medicine under the aegis of the Graduate School, College of Medicine & Life Sciences.


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Publications 

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