Edinburgh Research Explorer

Dr Richard Sharpe

(Former employee or visitor)

Profile photo

Willingness to take PhD students: Yes

Qualifications


1970   BSc (Hons Zoology) University of London,

1975   MSc, University of Brisol

1979   PhD, Council for National Academic Awards

 

Biography

I am based in the MRC/University Centre for Reproductive Health in Edinburgh where I head a research programme on developmental disorders of (mainly male) reproductive health.  I am a Professor in Edinburgh University College of Medicine & Veterinary Medicine.  My expertise and research interests cover sexual differentiation, development and puberty (and disorders thereof), fetal programming, endocrinology, the effects of lifestyle (smoking, obesity, diet, use of personal care products) and environmental chemical exposures on reproductive development and function.  I am increasingly interested in the inter-relationships between reproductive and wider aspects of health in relation to diet, obesity, inflammation and aging. I serve/have served on numerous advisory bodies in Europe and elsewhere, and as a member of Council for the Society for Endocrinology and as co-Chair of their Special Interest Group on ‘Endocrine disruptors’. I am a Deputy Editor of Human Reproduction.  I have published >350 papers and have an H index of 65 (ISI) 80 (Google).

Primary Research Interests

  • Fetal origins of the commonest human male reproductive disorders of newborn and young adult males (‘Testicular dysgenesis syndrome’)
  • Physiology, endocrinology, biochemistry and molecular biology of the development and function of the testis and male reproductive tract with respect to male reproductive health and fertility.
  • Regulation of spermatogenesis and sperm maturation. Disorders of spermatogenesis and sperm maturation. Detection of abnormalities in spermatogenesis.
  • Effects of environmental chemical exposures and lifestyle factors on testicular and reproductive tract development, spermatogenesis and fertility.
  • Fetal/neonatal determinants of adult reproductive health and function
  • Relationships between hormone exposures in fetal life and metabolic disorders, obesity/fat distribution and hormone levels in adulthood
  • Male reproductive toxicology

Research Focus and Aims

The overall aim is to identify how common) male reproductive disorders originate, what causes them and how could we prevent them? The disorders manifest at birth hypospadias, cryptorchidismor in young adulthood low sperm counts, testicular germ cell cancer (TGCC), reduced testosterone levels; they are remarkably common and/or increasing in incidence. Lifestyle/environmental factors must be responsible for this increase, implying there is potential for prevention, once causes are identified.

The ‘testicular dysgenesis syndrome’ (TDS) hypothesis proposes that these disorders can have a common fetal origin. We have identified that androgens from the fetal testis act within a critical time window – the ‘masculinisation programming window’ (MPW) – to program normal development and ultimate adult size of all male reproductive organs and anogenital distance (AGD). AGD provides a lifelong ‘read out’ of androgen exposure in the MPW and enables us to ‘look back in time’. The occurrence and severity of TDS disorders is related to AGD, pointing to their origin in the MPW because of deficient androgen action.

The primary goal of our research is to establish the pathways that govern normal testis development and function in fetal life that are vulnerable to disruption, resulting in TDS disorders. Once these pathways are identified, we study what sorts of factors relevant to human males (eg diet, lifestyle, chemical exposures) can impact them; this can form the basis for preventative strategies. A growing interest is to establish how fetal events determine adult testosterone levels, and if this then alters predisposition to develop obesity and related cardiometabolic disorders as an adult.

We are also interested in germ cell development during fetal life, and how exogenous factors (diet, lifestyle, exposures of the parents) may affect the epigenome of germ cells during the critical fetal period when epigenetic marks are erased and then reinstated. Can epigenetic changes to germ cells be induced as a result of eating a ‘Western’ style diet, and if so, can these be transmitted to the next generation and alter reproductive function or disease susceptibilities in offspring.

Our main research approach is to develop and use appropriate animal models. For example, we have developed and validated a rodent model of TDS based on fetal exposure to the environmental chemical, dibutyl phthalate. Other approaches use dietary modifications or the use of transgenic mice (collaboration with Prof Lee Smith). To ensure these animal studies are relevant to human males, we use human fetal testis tissue grafted into immunecompromised mice, as the grafted tissue develops normally (collaboration with Dr Rod Mitchell). These xenografts provide the main approach for studies into the origins of TGCC and its precursor (CIS cells) and provide a direct means of translating new findings from our animal studies to man.

By identifying when and how the fetal testis is sensitive to disruption, these studies will improve our ability to protect the human fetus during its critical phases and thus minimize risk of lateronset TDS and related disorders. This programme of work fits with theme 2 of the MRC strategic plan.

Video links/interviews describing the work of the Richard Sharpe Group

Interviews with Penelope Jagessar Chaffer on the masculinization process, fetal origins of male reproductive disorders and exposures to environmental chemicals

http://vimeo.com/14074824

http://vimeo.com/14070653

http://vimeo.com/17020615

http://vimeo.com/14067161

http://vimeo.com/14075337 

Using human tissue to study fetal origins of male reproductive disorders

http://www.youtube.com/watch?v=pIm6StLZ6tQ

British Nutrition Foundation: Perinatal effects of sex hormones in programming susceptibility to disease

http://www.youtube.com/watch?v=V9jhB-RVyFc&feature=share&list=UUN7jeypxEHJICJaC3-Ag5pA

CBS News 60 minutes: “Are phthalates safe?”

http://www.cbsnews.com/video/watch/?id=6512528n&tag=api

Stand-up comedy routine at Bright Club Edinburgh as part of the MRC Centenary celebrations in 2013

http://youtu.be/xFKDjS4efS

Current Projects

  • 2011 – 2016 Medical Research Council (Programme grant) Testis development and function in relation to disorders of reproductive and general health in males [~£2,800,000]. Role: PI
  • 2012 – 2015  Medical Research Council (Clinical Research Training Fellowship)
  • Environmental/dietary induced changes to the germline epigenome [£350,000]. Role:PI/Supervisor
  • 2013 Society for Reproduction & Fertility (SRF) Academic Scholarship. Prostaglandins and fetal germ cell differentiation and remethylation. [£9968]. Role: PI/Supervisor

Staff Group Members

Dr Sander van den Driesche, Postdoctoral Fellow
Dr Thomas Chambers, Clinical Research Fellow/PhD
Dr Karen Kilcoyne, MRC Centenary Fellow
Mr Chris McKinnell, Research Support
Mrs Sheila Macpherson, Research Support
Pablo Hurtado-Gonzalez, PhD Student
Maria Camacho Moll, PhD Student

Principal collaborators

Lee Smith, Rod Mitchell (CRH, Edinburgh)
Mandy Drake, (CVS, Edinburgh)
Hamish Wallace, Chris Kelnar (Sick Children’s Hospital, Edinburgh)
Paul Fowler, (Aberdeen)
Michelle Bellingham, Peter O’Shaughnessy (Glasgow)
Luzi Renata de Franca (Belo Horizonte, Brazil)
Serge Nef (Switzerland)
Nina Atanassova (Bulgaria)
Niels Skakkebaek, AnnaMaria Andersson, Katharina Main, Niels Jorgensen (Copenhagen, Denmark)
Jorma Toppari, (Turku, Finland)
Manuel TenaSempere(Cordoba, Spain)
Bernard Jégou (Rennes, France)
Shanna Swan (Rochester, USA)

Current positions of responsibility

Convenor, Postgraduate Studies Committee, CRH
Member of expert panel for Sense about Science UK
Member, British Nutrition Foundation task force on developmental programming of later disease
Deputy Editor of Human Reproduction
Member, ‘Clinical & Environmental health research’ panel, Academy of Finland

Awards/Invitations

  • 2010    Elected to the Fellowship of the Royal Society of Edinburgh (FRSE)2010   Invited to give presentation to UK Advisory Committee on Hazardous Substances on ‘Endocrine disruption and human health’
  • 2010   Invited to give presentation to The UK Royal Society of Chemistry’s Toxicology Group & Environment & Health Safety Committee on ‘Exposure to chemical mixtures and human reproductive disorders’
  • 2010   BSc Reproductive Honours research project report by Miss Polly Dunne in my group was awarded the Society for Endocrinology prize for undergraduate achievement for the best dissertation on an endocrinology topic
  • 2010   Invited to give presentation to the British Science Festival (Birmingham) on use of xenografts of human fetal testis tissue for identifying the fetal origins of male reproductive disorders.
  • 2011   Invited presentation on phthalate effects on the developing male reproductive system (webcast: http://www.cpsc.gov/about/cpsia/chap1111.html) to the US Consumer product safety commission: chronic hazard advisory panel (CHAP). Washington, USA.
  • 2012   Invited to give presentation to the Cheltenham Science Festival on the contribution of environmental/lifestyle factors to earlier onset of puberty in humans
  • 2013   Invited to give presentation to the American Association for the Advancement of Science (AAAS) meeting in Boston, USA (February)on human exposure to bisphenol A and its potential impacts on health
  • 2013   Invited to give presentation to the European Parliament (Science and Technology Options Assessment: STOA) on ‘Endocrine Disruption: what’s it all about’
  • 2014   Invited participant for meeting in Downing Street with UK Government Chief Scientific Adviser to discuss ‘Endocrine disruptors’

Interactions with the Media

  • Television appearances/interviews for main BBC/ITV/Sky News, for Danish television news and two Danish documentaries. Numerous other TV appearances/interviews. Most recent participations were in the French production ‘Men in Danger
  • [http://www.filmakers.com/index.php?a=filmDetail&filmID=1558], winner of the Prix Europa in 2008 for Best Current Affairs Program; the Norwegian film ‘Underkastelsen’ (2010) English title: ‘Submission: the defence of the unborn’ (Dir: Stefan Jarl; http://www.underkastelsen.se/); CBS News 60 minutes programme on ‘Phthalates: are they safe?’ (2010) [http://www.cbsnews.com/video/watch/?id=6512528n&tag=api]; the UK production ‘Toxic baby’ (2011) (Dir: Penelope Jag; http://www.youtube.com/watch?v=zsO663N31jY&feature=related).
  • Numerous radio interviews for NBC in USA, Radio stations in Canada, Australia, Jamaica, Denmark, Germany, Switzerland and France, BBC World News, BBC Radio 2/Radio 5, Radio 4 (Today programme, File on 4,), Radio Scotland, Radio 1 (Ireland), several local radio stations in UK.
  • Invited author of articles on male reproductive health problems for The Daily Telegraph Science page, The Scotsman in their series on male health problems, and for the Newswatch page of the Edinburgh Evening News. Invited author of article on Hormonally active pollutants for Newsweek (Alp Action).
  • Major interviews on a variety of topics related to male reproductive health for in-depth articles published in: New Yorker magazine, Town & Country magazine, Science News, ENDS magazine, The Independent, The Times, The Guardian, The Daily Telegraph, The Daily Mail, The Daily Express, The Scotsman, The Sunday Times, Scotland on Sunday etc. plus many popular men's and women's magazines (even one in Playboy!). Numerous ad hoc interviews for UK and international newspapers on subjects of current interest related to reproductive health. 

Reports/Expert Working Groups

  • Co-writer of report prepared for the European Science Foundation on Male reproductive health: its impact in relation to general wellbeing and low European fertility rates, published September 2010, Science Policy briefing No: 40. http://www.esf.org/publications/medical-sciences.html
  • Member of the British Nutrition Foundation task force on early developmental programming and later disease. Published May 2013. http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1444336789,descCd-buy.html
  • Member of the WHO (World Health Organisation)/FAO (Food and Agriculture Organisation) expert committee for evaluation of the health risks and research priorities on bisphenol A. ftp://ftp.fao.org/ag/agn/agns/BPA_Summary_Report.pdf
  • Invited to give 1 hour presentation (web-casted) on ‘Phthalate effects on the fetal testis: mechanism of action and species and age-related differences’ to the US Consumer product safety commission: chronic hazard advisory panel (CHAP). Washington, USA. November 2011. http://www.cpsc.gov/about/cpsia/chap1111.html
  • Co-writer of report prepared for the European Environment Agency (EEA) on The impacts of endocrine disrupters on wildlife, people and their environments. EEA technical report No 2/2012; ISSN 1725-2237. May 2012
  • Co-author of report for the Italian Society of Toxicology (SITOX) Task Force on ‘Endocrine disrupting chemicals expert consensus documents’. Presented to the EU, May 2013.
  • Co-author of report on Chemical Exposures During Pregnancy; dealing with potential, but unproven, risks to child health. Scientific impact paper No 37 for the UK Royal College Of Obstetricians & Gynaecologists. May 2013. http://www.rcog.org.uk/womens-health/clinical-guidance/chemical-exposures-during-pregnancy-scientific-impact-paper-37

ID: 316403