Prof Norah Spears
I am a reproductive biologist, with a primary focus on investigating how chemotherapy treatment can impact on subsequent fertility.
- 2014 - present: Professor of Reproductive Physiology, University of Edinburgh, 2014 to present
- 2002 - 2014: Reader, University of Edinburgh, 2002 to 2014
- 1994 - 2002: Royal Society University Research Fellow
- 1990 - 1994: MRC Training Fellowship
- 1987 - 1988: Postdoctoral Scientist, University of Berkeley at California
- 1986: DPhil, University of Oxford
- 1982: BSc (Hons) in Ecological Sciences, University of Edinburgh
My laboratory has two current areas of research:
- Due to the improved survival rates from many cancers, there is increasing attention on how chemotherapy treatment can adversely affect the subsequent quality of life. For young people, among the most important of these are effects on fertility, yet the primary site of action of chemotherapeutic drugs on the gonads is still unknown. This hampers the development of treatments to mitigate these adverse effects. We are investigating the direct effect of some of the drugs most commonly used to treat young patients. The first aim of our work is to determine effects of the drugs, working on ovary and testis (see Figure 1, and book ‘Cancer treatment and the ovary: Clincial and laboratory analysis of ovarian toxicity. Eds RA Anderson and N Spears. 2015, Elsevier; ISBN 9780128015919 / 9780128016015). Work is also examining whether it is possible to protect the gonad against such damage. As part of this work, I have been involved in setting up Edinburgh Fertility Preservation, a consortium of clinicians and scientists working together to optimise fertility for children and young adults with cancer: Edinburgh Fertility Preservation
Work in my laboratory also examines ovary development in more detail, including follicle formation, growth initiation and how interactions between follicles can regulate the number of oocytes ovulated each cycle. Regulated development of a species-specific number of ovarian follicles to the preovulatory stage each menstrual or oestrous cycle, potentially available for fertilization, is clearly vital to the successful reproduction of a female mammal. This is achieved by the continual development of a much larger number of follicles, with most undergoing follicular atresia and dying: the means by which this is achieved is still unclear. Our work examines interactions between follicles as they grow and develop, and how these interactions can affect (a) growth initiation of follicles; and (b) whether the 'dominant' follicles, which will successfully develop to the preovulatory stage, actively suppress growth in the remaining 'subordinate' follicles. As a consequence of that work, we have recently found that ovarian follicles have cells (both endothelial and neuronal) embedded within their outer layers, that grow processes over other follicles with which they come in contact (see Figure 2), and are examining how the processes can influence follicle-follicle communication. Much of our work has involved developing tissue culture techniques that support physiological development of the gonads in vitro: watch our video on Culture and Co-Culture of Mouse Ovaries and Ovarian Follicles
Ectopic Pregnancy and epithelial to mesenchymal transition video with Heather Flanagan (PhD student):
- Video: Ectopic Pregnancy and epithelial to mesenchymal transition- is there a link
- 'Ectopic Pregnancy and epithelial to mesenchymal transition- is there a link'
Equality and Diversity work
I have a strong interest in equality and diversity issues, including improving the gender balance in STEM subjects at Universities. As part of that, I chair Biomedical Sciences’ Academic Opportunities Committee, and spearheaded our current Athena SWAN silver award.
- Kathleen Duffin ( ECAT CRUK Clinical Research Fellow)
- Federica Lopes (Postdoctoral Fellow)
- Heather Flanagan (PhD Student)
- Caroline Allen (PhD Student)
- Prof Richard Anderson, University of Edinburgh
- Prof Alistair Elfick, Engineering, University of Edinburgh
- Prof Kate Hardy, Imperial College, London
- Dr Richard Lea, University of Nottingham
- Dr Rod Mitchell, University of Edinburgh
- Prof Evelyn Telfer, University of Edinburgh
Anwar N, Qureshi IZ, Spears N, Lopes F (2020) In vitro administration of sodium arsenite in mouse prepubertal testis induces germ cell loss and apoptosis. Toxcicology In Vitro (in press).
Tholeti P, Uppangala S, Bhat V, Udupa KS, Kumar V, Patted S, Natarajan P, Spears N, Kalthur G, Woodruff TK, Adiga SK (2020) Oncofertility: knowledge, attitudes, and barriers among Indian oncologists and gynecologists. Journal of Adolescent and Young Adult Oncology doi: 10.1089/jayao.2020.0034.
Allen CM, Lopes F, Mitchell RT, Spears N (2020) Comparative gonadotoxicity of the chemotherapy drugs cisplatin and carboplatin on prepubertal mouse gonads. Molecular Human Reproduction 26: 129-140. doi: 10.1093/molehr/gaaa008.
Lopes F, Liu J, Morgan S, Matthews R, Nevin L, Anderson RA, Spears N (2020) Single and combined effects of cisplatin and doxorubicin on the human and mouse ovary in vitro. Reproduction 159: 193-204. doi: 10.1530/REP-19-0279.
Spears N, Lopes F, Stefansdottir A, Rossi V, De Felici M, Anderson RA, Klinger FG (2019) Ovarian damage from chemotherapy and current approaches to its protection. Human Reproduction Update (2019). 25: 673-693. doi: 10.1093/humupd/dmz027.
Allen CM, Lopes F, Mitchell RT, Spears N (2018) How does chemotherapy treatment damage the prepubertal testis? Invited review. Reproduction 156; R209–R223. doi: 10.1530/REP-18-0221.
Zand E, Fathi R, Nasrabadi MH, Atrabi MJ, Spears N, Akbarinejad V (2018) Maturational genes upregulation and mitochondrial activity enhancement in mouse in-vitro matured oocytes applying granulosa cells conditioned medium. Zygote 26: 366-371. doi: 10.1017/S0967199418000333
Smart E#, Lopes F#, Rice S, Nagy B, Anderson RA, Mitchell RT†, Spears N† (2018) Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis. Scientific Reports 8(1):1773. doi: 10.1038/s41598-018-19761-9 (#,†: both authors contributed equally to the work)
Lopes F, Smith R, Mitchell RT, Spears N (2016) Irinotecan metabolite SN38 results in germ cell loss in the testis but not in the ovary of prepubertal mice. Mol Human Reprod; 22; 745-755. doi: 10.1093/molehr/gaw051
Stefansdottir A, Johnston ZC, Powles-Glover N, Anderson RA, Adams IR, Spears N (2016) Etoposide Damages Female Germ Cells in the Developing Ovary. BMC Cancer, 16; 482. DOI 10.1186/s12885-016-2505-9.
Lopes F, Spears N, Anderson RA. (2016) Effects of chemotherapeutic treatment on female reproductive function. Current Trends in Clinical Embryology 2(5); 158-166.
Cancer treatment and the ovary: Clincial and laboratory analysis of ovarian toxicity. Eds RA Anderson and N Spears. 2015, Published by Elsevier; pp166; ISBN 9780128015919 / 9780128016015
Morgan S, Spears N (2015) In vitro models of ovarian toxicity. In “Cancer treatment and the ovary: Clincial and laboratory analysis of ovarian toxicity”. Eds RA Anderson and N Spears. pp79-92; Elsevier.
Anderson RA, Mitchell RT, Kelsey TW, Spears N, Telfer EE, Wallace WHB (2015) Cancer treatment and fertility: strategies for fertility preservation in children and young adults. Lancet Diabetes and Endocrinology, 3; 556-567. doi: 10.1016/S2213-8587.
Morgan S, Campbell L, Allison V, Murray A, Spears N. (2015) Culture and co-culture of mouse ovaries and ovarian follicles. Journal of Visualised Experiments (JoVE), Issue 97, DOI 10.3791/52458 (video URL: http://www.jove.com/video/52458).
Stefansdottir A, Fowler PA, Powles-Glover N, Anderson RA, Spears N (2014) Use of ovary culture techniques in reproductive toxicology. Reproductive Toxicology, 49; 117-135; DOI http://dx.doi.org/doi:10.1016/j.reprotox.2014.08.001.
Lopes F, Smith R, Anderson RA, Spears N. (2014) Docetaxel induces moderate ovarian toxicity in mice, primarily affecting granulosa cells of early growing follicles. Molecular Human Reproduction, 20; 948-959; DOI 10.1093/molehr/GAU057.
Morgan S, Lopes F, Anderson RA, Gourley C, Spears N. (2013) Cisplatin and Doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin. PlosOne 8:e70117. doi: 10.1371/journal.pone.0070117.
Davidson B, Murray AA, Elfick A, Spears N. (2013) Raman micro-spectroscopy can be used to investigate the developmental stage of the mouse oocyte. PlosOne 8:e67972. doi: 10.1371/journal.pone.0067972.
Campbell L, Trendell J, Spears N. (2013) Identification of cells migrating from the thecal layer of ovarian follicles. Cell and Tissue Research 353; 189-194.
Filis P, Kind P, Spears N. (2013) Implantation failure in mice with a disruption in Phospholipase C beta 1 gene: lack of embryonic attachment, aberrant steroid hormone signalling and defective endocannabinoid metabolism. Molecular Human Reproduction 19; 290-301.
Morgan S, Anderson RA, Wallace H, Gourley C, Spears N (2012). How do chemotherapeutic agents damage the ovary? Human Reproduction Update 18; 525-535.
Davidson B, Spears, N, Murray AA, Elfick A (2012) The changing biochemical composition and organisation of the murine oocyte and early embryo as revealed by Raman spectroscopic mapping. J Raman Spectroscopy 43; 24-31.
McNeilly J, Watson E, Brown Y, Murray AA, Spears N, McNeilly A (2010). Decreased oocyte Dazl expression results in increased litter size by modulating FSH induced follicle growth. Biology of Reproduction 85; 584-593.
Childs AJ, Bayne RAL, Murray AA, Martins da Silva SJ, Collins CS, Spears N, Anderson RA. (2010) Differential expression and regulation by activin of the neurotrophins BDNF and NT4 during human and mouse ovarian development. Developmental Dynamics 239; 1211-1219.
Filis P, Lannagan T, Thomson A, Murray AA, Kind PC, Spears N. (2009) Phospholipase C beta-1 signalling affects reproductive behaviour, ovulation and implantation. Endocrinology 150; 3259-3266.
Paul C, Murray AA, Spears N, Saunders PTK. (2008) A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction 136, 73-84.
Murray, AA, Swales, AKE, Smith, RE, Molinek, MD, Hillier, SG, Spears, N. (2008) Follicular growth and oocyte competence in the in vitro cultured mouse follicle: effects of gonadotrophins and steroids. Mol Human Reprod 14, 75-83.
Information for students:
Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here