Dr Rod Mitchell
Rod Mitchell's research focuses on the developing human testis in relation to fertility preservation, disorders of sexual development (DSD) and testicular cancer.
Rod is a Research Group Leader within the MRC Centre for Reproductive Health at the University of Edinburgh. He is also a Consultant Paediatric Endocrinologist at The Royal Hospital for Sick Children in Edinburgh.
His research interests are focused on the role of the germ-stem cell niche in the postnatal testis and the effects of exposure to pharmaceuticals (including chemotherapy and analgesics) on germ cell development and future fertility potential. He has a particular focus on clinical and research aspects of fertility preservation for young males treated for cancer. Edinburgh recently became the first UK Centre to develop a fertility preservation programme to store testicular tissue from young boys with cancer prior to their treatment, as part of the 'Edinburgh Fertility Preservation’ programme, for which Rod is the lead for male fertility preservation. He combines his research programme with a clinical role as a Consultant Paediatric Endocrinologist.
- Karen Kilcoyne (Post-Doc)
- Federica Lopes (Post-Doc)
- Melissa Tharmalingam (PhD student)
- Marsida Hutka (PhD student)
- Gabriele Matilionyte (PhD student)
- Joni MacDonald (former Post-Doc – currently at Roslin Institute)
- Maria-Elena Camacho-Moll (former PhD student – currently at University of Leon, Mexico)
Fertility preservation in childhood cancer survivors
My research interests include fertility preservation in the pre-pubertal testis and this focuses on developing strategies for removing and storing testis tissue from patients prior to potentially sterilizing treatments in order that germ cell development can be achieved using in-vitro or in-vivo techniques. We have recently become the first UK centre to establish a fertility preservation programme to store testicular tissue from young cancer patients prior to their treatment. This programme in males, combined with our well-established fertility preservation programme for females, has resulted in the establishment of a collaboration of scientists and clinicians working as part of the 'Edinburgh Fertility Preservation’ programme of which I am the lead for male fertility preservation. This unique collaboration combines clinical and laboratory research aimed at optimising fertility for children and young adults with cancer. We are also a full partner in the EU funded FP7 Marie Curie ITN entitled 'GROWSPERM' aimed at co-ordinating research into male fertility preservation for boys with cancer. We also receive funding for our male fertility preservation work from Children with Cancer UK.
The germ stem cell niche in the human fetal testis and the origins of testicular cancer
My research group also focuses on fetal development of the testis and particularly that of germ cells in relation to the origins of testicular cancer. Testicular cancer is thought to result from disrupted development of germ cells during fetal life which results in pre-malignant germ cell neoplasia in situ (GCNIS) cells. The precise mechanisms of how this occurs are unknown. Understanding the origins of testicular cancer and developing fertility preservation strategies require further understanding of the germ stem cell niche and we hope that by using the models described above we will learn more about the interactions between germ cells and their surrounding cells during testis development. Our research in this area has recently demonstrated the relationship between the stage of germ cell development and its relationship to invasive potential in testicular cancer.
The effect of exposure to endocrine disruptors on development of the human fetal testis
Fetal testis development may potentially be disrupted by environmental ‘endocrine disruptors’ and genetic factors and may increase the risk of developing testicular cancer. These factors are being investigated using a variety of animal and human models of testis development. Our recent research in this area has demonstrated that paracetamol (acetaminophen) exposure can reduce testosterone production in the human fetal testis.
Sources of Funding
- Children with Cancer UK (CWCUK) – Project Grant ‘Fertility preservation in pre-pubertal boys treated for cancer during childhood’ £249,854 (2016-2019). Role – PI
- Medical Research Council Programme Grant ‘Androgens: unlocking the key drivers of male health and wellbeing’ £2,180,000 – (2016-2021). Role – Co-I
- FP7- PEOPLE-2013-ITN (7 European Centres) ‘GROWSPERM’ £2,060,000 – (2014-2018). Role – Full Partner/PI
- Wellcome Trust Intermediate Clinical Fellowship ‘The germ-stem cell niche in the human fetal testis’ £1,036,886 (2012-2016). Role – PI
Ben Maamar M, Lesné L, Hennig K, Desdoits-Lethimonier C, Kilcoyne KR, Coiffec I, Rolland AD...Mitchell RT...Mazaud-Guittot S, Jégou B. Ibuprofen results in alterations of human fetal testis development. Scientific Reports. 2017 7:44184.
van den Driesche S, Kilcoyne KR, Wagner I, Rebourcet D, Boyle A, Mitchell RT, McKinnell C, Macpherson S, Donat R, …Sharpe RM. Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window. JCI Insight. 2(6):e91204. 2017
Mitchell RT, Sun A, Mayo A, Forgan M, Comrie A, Gillett PM. Coeliac screening in a Scottish cohort of children with type 1 diabetes mellitus: is DQ typing the way forward? Archives of Disease in Childhood. 101(3):230-3. 2016
Dean A, van den Driesche S, Wang Y, McKinnell C, Macpherson S, Eddie S, Kinnell H, …Mitchell RT, Anderson RA, Sharpe RM. Analgesic exposure in pregnant rats affects fetal germ cell development with intergenerational reproductive consequences. Scientific Reports. 2016
Rebourcet D, Wu J, Cruickshanks L, Smith SE, Milne L, Fernando A, Wallace RJ… Mitchell RT, O’Shaughnessy PJ and Smith LB. Sertoli cells modulate testicular vascular network development, structure and function to influence circulating testosterone concentrations in adult male mice. Endocrinology. 157(6):2479-88. 2016
Lopes F, Smith R, Nash S, Mitchell RT and Spears N. Irinotecan metabolite SN38 results in germ cell loss in the testis but not in the ovary of prepubertal mice. Mol Hum Reprod. 22(11):745-755. 2016.
van den Driesche S, Macdonald J, Anderson RA, Johnston ZC, Chetty T, Smith LB, Mckinnell C, Dean A, Homer NZ…Mitchell RT. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model. Science Translational Medicine. 7(288): p. 288ra80. 2015.
van den Driesche S, McKinnell C, Calarrão A, Kennedy L, Hutchison GR, Hrabalkova L, Jobling MS, Macpherson S, Anderson RA… Mitchell RT. Comparative effects of Di(n-Butyl) phthalate exposure on fetal germ cell development in the rat and in human fetal testis xenografts. Environmental Health Perspectives 123(3): 223-233. 2015.
Anderson RA*, Mitchell RT*, Thomas W Kelsey, Norah Spears, Evelyn E Telfer, W Hamish B Wallace. Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults. The Lancet Diabetes and Endocrinology. 3(7):556-67. 2015. (* denotes equal contribution)
Picton HM… Jahnukainen K, Kliesch S, Mitchell RT, Pennings G, Rives N, Tournaye H, van Pelt AM, Eichenlaub-Ritter U, Schlatt S; A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys. ESHRE Task Force on Fertility Preservation in Severe Diseases. Human Reproduction. 30(11):2463-75. 2015
A Jørgensen, JE Nielsen, S Perlman, L Lundvall, RT Mitchell, A Juul and E Rajpert-De Meyts. Ex vivo culture of human fetal gonads: Manipulation of meiosis signalling by retinoic acid treatment disrupts testis development. Human Reproduction. 30(10):2351-63. 2015
Mitchell RT, Mungall W, McKinnell C, Sharpe RM, Cruickshanks L, Milne L, and Smith LB. Anogenital distance (AGD) plasticity in adulthood: Implications for its use as a biomarker of fetal androgen action. Endocrinology 1(1):24-31. 2015.
Willems A, Roesl C, Mitchell RT, Milne L, Jeffery N, Smith S, Verhoeven G, Brown P and Smith LB. Sertoli Cell Androgen Receptor Signalling in Adulthood is Essential for Post-Meiotic Germ Cell Development. Molecular Reproduction and Development. 82(9):626-7. 2015.
O’Hara L, McInnes K, Simitsidellis I, Morgan S, Atanassova N, Slowikowska-Hilczer J, Kula K, Szarras-Czapnik M… Mitchell RT, Smith LB. Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men. The FASEB Journal 29(3):894-910. 2015.
Mitchell RT, Camacho-Moll M, Macdonald J, Anderson RA, Kelnar CJH, O’Donnell, M, Sharpe RM Smith LB, Grigor KM, Wallace WHB et al. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential. Modern Pathology. 27(9):1255-66. 2014.
Rebourcet D, O’Shaughnessy PJ, Pitetti J-L, Monteiro A, O’Hara L, Milne L, Tsai Y-T, Cruickshanks L …Mitchell RT…. Smith LB. Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis. Development. 141(10):2139-49. 2014
Mitchell RT, Sharpe RM, Anderson RA, McKinnell C, Macpherson S, Smith LB, Wallace WHB, Kelnar C, and van den Driesche S. Diethylstilboestrol exposure does not reduce testosterone production in human fetal testis xenografts. PLoS ONE. 8(4): e61726. 2013
Mitchell RT, Childs AJ, Anderson RA, van den Driesche S, Saunders PTK, McKinnell C, Wallace WHB, Kelnar CJH, Sharpe RM. Do phthalates affect steroidogenesis by the human fetal testis? Exposure of human fetal testis xenografts to di-n-butyl phthalate. Journal of Clinical Endocrinology and Metabolism. 97(3): E341-8. 2012
Mitchell RT, Saunders PTK, Childs AJ, Cassidy-Kojima C, Anderson RA, Wallace WH, Kelnar CJ, Sharpe RM. Xenografting of human fetal testis tissue: a new approach to study fetal testis development and germ cell differentiation. Human Reproduction. 25(10): 2405-2414. 2010
Mitchell RT, Cowan G, Morris KD, Anderson RA, Fraser HM, Mckenzie KJ, Wallace WHB, Kelnar CJH, Saunders PTK and Sharpe RM. Germ cell differentiation in the marmoset (Callithrix jacchus) during fetal and neonatal life closely parallels that in the human. Human Reproduction. 23(12): 2755-65. 2008
Honours and Awards
- Society for Reproduction and Fertility – New Investigator Award - 2016
- Royal College of Paediatrics and Child Health – UK Young Investigator of the Year – 2013
Public Engagement Activities
- Fertility Preservation – TV coverage – BBC Reporting Scotland
- Fertility Preservation – Newspaper coverage - Scotsman
- Fertility Preservation - Newspaper coverage - Herald Scotland
- Fertility Preservation – Public Information Video
- Effects of analgesic exposure on the fetal testis – TV coverage BBC Breakfast
- Public Lecture – Testosterone and Male Health
- CRH Postgraduate Studies Committee
- Reproductive Biology MSc Exam Board
- Internal PhD Examiner
- Convenor of FAME (part of ECAT) for Clinical Academic trainees in Edinburgh
- Lead for male fertility preservation clinical and research programme
External Examiner for PG Certificate of Child Health, University of Glasgow
External PhD examiner – Rennes University, 2015; Brussels University, 2016; Turku University, 2017
- Programme Organising Committee for European Congress of Endocrinology
- Editorial Board Member for Frontiers in Endocrinology:Reproduction Journal
- Jan-Bernd Stukenborg – Karolinska Institute, Stockholm
- Donal O’Carroll – Centre for Regenerative Medicine, Edinburgh
- Norah Spears – Centre for Integrative Physiology, Edinburgh
- Richard Anderson – Centre for Reproductive Health, Edinburgh
- Hamish Wallace – Royal Hospital for Sick Children, Edinburgh