Professor Rod Mitchell
Research interests, current research projects and external grants.
Professor Rod T Mitchell
Professor of Developmental Endocrinology
- Consultant Paediatric Endocrinologist
- Principal Investigator
Contact details
Address
- Street
The Queen’s Medical Research Institute
Edinburgh BioQuarter
47 Little France Crescent- City
- Edinburgh
- Post Code
- EH16 4TJ
Availability
Department of Paediatric Endocrinology
Royal Hospital for Children and Young People
Edinburgh BioQuarter
50 Little France Crescent
Edinburgh
EH16 4TJ
Research Interests
The developing human testis in relation to fertility preservation, disorders of sex development (DSD) and testicular cancer.
Current Research Projects
1) Fertility preservation in childhood cancer survivors
Our research group interests include fertility preservation in children with cancer 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.
To view the above video, please click here
In 2015, we became the first UK research group 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 for which Professor Mitchell is 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 have received funding for our male fertility preservation work from Children with Cancer UK, Wellcome and UKRI.
Visit the Edinburgh Fertility Preservation website
Key References:
- Mulder RL et al; PanCareLIFE Consortium. Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncology. 2021 Feb;22(2):e57-e67. doi: 10.1016/S1470-2045(20)30582-9.
- Tharmalingam MD et al. Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer. BMC Medicine. 2020 Dec 4;18(1):374. doi: 10.1186/s12916-020-01844-y.
- Tian En L, Brougham MFH, Wallace WHB, Mitchell RT. Impacts of platinum-based chemotherapy on subsequent testicular function and fertility in boys with cancer. Human Reproduction Update. 2020 Nov 1;26(6):874-885. doi: 10.1093/humupd/dmaa041.
- Anderson RA et al. Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults. Lancet Diabetes and Endocrinology. 2015 Jul;3(7):556-67. doi: 10.1016/S2213-8587(15)00039-X.
2) The germ stem cell niche in the human fetal testis and the origins of testicular cancer
Our research is also focused on fetal development of the testis and particularly that of germ cells in relation to the origins of testicular cancer and infertility. 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 that we will learn more about the interactions between germ cells and their surrounding cells during testis development. Our research on origins of testicular cancer has demonstrated the relationship between the stage of germ cell development and their invasive potential. We also show that alteration of key signalling pathways and repression of transcription factors can induce testicular dysgenesis in the human fetal gonad.
Key References:
- Smart E et al. Reconstitution of rat fetal testis during the masculinisation programming window induces focal dysgenesis consistent with testicular dysgenesis syndrome. Scientific Reports. 2020 Nov 4;10(1):19022. doi: 10.1038/s41598-020-75803-1.
- Camacho-Moll ME et al. The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells. BMC Cancer. 2019 Nov 19;19(1):1124. doi: 10.1186/s12885-019-6340-7.
- Jørgensen A et al. Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis. Cell Reports. 2018 Nov 13;25(7):1924-1937.e4. doi: 10.1016/j.celrep.2018.10.064.
- Macdonald J et al. DMRT1 repression using a novel approach to genetic manipulation induces testicular dysgenesis in human fetal gonads. Human Reproduction. 2018 Nov 1;33(11):2107-2121. doi: 10.1093/humrep/dey289.
3) The effect of exposure to endocrine disruptors on development of the human fetal testis
Fetal testis development may potentially be impaired by exposure to environmental endocrine disrupting chemicals (EDCs) and this can have consequences for subsequent reproductive health in males. Potential EDCs include plasticisers, pesticides and pharmaceuticals and we are investigating the impact of a variety of these chemicals using our experimental animal and human models of testis development. Our recent research in this area has focused on effects of exposure to paracetamol (acetaminophen) on male reproductive development. We have shown that exposure to paracetamol can reduce the number of germ cells and impair testosterone production in human fetal testis tissues, which could affect reproductive health in males in later life.
Key References:
- Zafeiri A et al. Maternal over-the-counter analgesics use during pregnancy and adverse perinatal outcomes: cohort study of 151 141 singleton pregnancies. BMJ Open. 2022 May 3;12(5):e048092. doi: 10.1136/bmjopen-2020-048092.
- Bauer AZ et al. Paracetamol use during pregnancy - a call for precautionary action. Nature Reviews Endocrinology. 2021 Dec;17(12):757-766. doi: 10.1038/s41574-021-00553-7.
- Hurtado-Gonzalez P et al. Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems. Environ Health Perspect. 2018 Apr 16;126(4):047006. doi: 10.1289/EHP2307.
- van den Driesche S, Macdonald J, Anderson RA, Johnston ZC, Chetty T, Smith LB, Mckinnell C, Dean A, Homer NZ, Jorgensen A, Camacho-Moll ME, Sharpe RM, Mitchell RT. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model. Science Translational Medicine. 2015 May 20;7(288):288ra80. doi: 10.1126/scitranslmed.aaa4097.
Staff/Group members
David Greenald – Lab Manager/Senior Technician
Peter Nagle – Post-Doctoral Fellow
Michael Rimmer – ECAT Clinical Fellow
Ruth Kwong – Clinical Fellow (visiting)
Associate member: Federica Lopes – Post-Doctoral Fellow
Current PhD/MD students
Grace Forsyth – PhD Student
Iris Sanou – PhD Student (Netherlands)
Mariska Schroeder - PhD Student (Netherlands, Visiting)
Current and recent grants
UKRI Future Leader Fellowship – £1.2M (2019 – 2024)
Role: Principal Investigator
Protecting spermatogonial stem cells from chemotherapy-induced damage for fertility preservation in childhood cancer.
ESHRE Research Grant - £65,000 (2022– 2024)
Role: Principal Investigator
Fertility preservation in (peri)pubertal boys: Developing an approach for simultaneous
cryopreservation of sperm and spermatogonial stem cells from testicular biopsies
ESHRE Research Grant - £177,000 (2022 – 2024)
Role: Co-Investigator
Exploiting multi-omics to assess and map the fertility potential of cryopreserved testicular tissues
Australian National Health and Medical Research Council - £289,000 (2019 – 2022)
Role: Co-Investigator
The importance of classical versus backdoor androgen production pathways in masculinisation, fertility and lifelong male health
Children with Cancer UK - Project Grant – £249,449 (2016-2019)
Role: Principal Investigator
Fertility Preservation project. Clinical project for testis tissue cryopreservation for children with cancer, combined with laboratory research project aimed at preserving fertility during chemotherapy treatment
MRC Programme Grant – £2.18m (2016 – 2021)
Role: Co-Investigator
The role of androgens in health and disease. Principal Investigator – Professor Lee Smith, MRC Centre for Reproductive Health, Edinburgh
Michelson Grant in Reproductive Biology Project Grant - £730,000 (2016 – 2019)
Role: Co-Investigator
Translation of an androgen miRNA sterilant: pre-clinical validation & a clinical trial in cats & dogs
FP7 EU Initial Training Network - £2.5m (2014 – 2018)
Role: Principal Investigator
European collaboration for joint PhD studentships (x8) and post-doctoral fellowships (x2) shared between centres in 6 EU countries. Title: GROWSPERM. Fertility Preservation project
Wellcome Trust Intermediate Clinical Fellowship - £1.03m (2012 – 2017)
Role: Principal Investigator
The germ stem cell niche and the origins of testicular germ cell tumours
Selected recent publications
Key references included in ‘Current Research Projects’. For a full list of publications please click here
Lab media
Fertility preservation in boys:
Birth of live monkey following prepubertal testicular transplant
Painkillers in pregnancy and fertility
70 Years of NHS Scotland - Looking after patients from cradle to grave
Paracetamol in pregnancy
Current external activities
European Society of Human Reproduction and Embryology
- Senior Deputy ESHRE SIG Fertility Preservation
European Space Agency
- Expert Working Group – White Paper ‘RoadMap’ for Reproduction and Development
Royal College of Paediatrics and Child Health (RCPCH)
- Academic Training Representative, South East Scotland
Society for Reproduction and Fertility
- SRF Council Member, Public Engagement and Membership Committee
UK Research and Innovation (UKRI)
- FLF – Peer Review Council
University of Glasgow
- External Examiner for PG Certificate of Child Health
Journal of Paediatric Endocrinology and Metabolism
- Associate Editor
Frontiers in Toxicology: Reproductive and Developmental Toxicology
- Associate Editor
Principal Collaborators
Jan-Bernd Stukenborg - Karolinska Institute, Sweden
Anne Goriely - University of Oxford, UK
Norah Spears - University of Edinburgh, UK
Lee Smith – University of Newcastle, Australia
Jennifer Adibi – University of Pittsburgh, US
Ans van Pelt - UMC Amsterdam, Netherlands
Links
