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Associate Professor Jeremy Thompson
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My research lies in discovering the metabolic determinants of developmental potential within mammalian oocytes and embryos, as well as the influence of specific growth factors in determining these. I conduct this research primarily in cattle and mouse models, plus collaboration in human oocyte competence with Prof. Johan Smits at VUB in Brussels. Along with long standing collaborations on the roles of oocyte secreted factors and cytokines in determining oocyte competence, I am also focussed on how compromised maternal peri-conception metabolic environments, such as hyperglycaemia and hypoxia, influence oocyte and embryo metabolism leading to adverse developmental outcomes, including research collaboration with Prof T Monro (Inst. Photonics and Sensing, U. of Adelaide) on micronutrient and ionic sensing during early development
Early Development Group Members
1980 B.Sc. The University of Adelaide
1981 - B.Sc. (Hons) Thesis title: The effect of the social environment on the gonadal
1986 - Ph.D. Thesis title: Studies on the fertilization in sheep using in vitro methods
Awards & Achievements
1989 - New Zealand Society of Animal Production's Young Members Award
1993 - Recipient Prince and Princess of Wales Science Award. Administered by the Royal Society of New Zealand. For Travel to the United Kingdom for study (1500 NZD)
1993 - McLaughlin Trust Award. Administered by the Trustees. For Travel to the United Kingdom for study
1993 - AgResearch Travel Fellowship. Provided by AgResearch New Zealand as a competitive fund for Sabbatical support (20,000 NZD)
2000 - New Zealand Society of Animal Production Animal Science Award
2007 - Mentorship Award
2011 - Mentorship Award
2013 - Made a Fellow of the Society for Reproductive Biology
My overall research interest lies in the relationship between micro-environmental, especially nutritional factors, surrounding the cumulus-oocyte complex and during early embryo development, in both the in vivo (follicular/oviduct/uterine) or in vitro environment, and the developmental competence of the oocyte. This encompasses the following research:
Hypoxia, Hypoxia inducible factors and their role in reproduction
My laboratory has had a long standing interest in the role of oxygen concentration in regulating events within the female reproductive tract. This is primarily because both oocytes (within follicles) and pre-implantation stage embryos (especially within the uterus) develop in what is normally considered low oxygen concentration environments. We have focussed on the role of the transcription factor, Hypoxia Inducible Factor, in regulating a number of transitional events, such as follicle antrum formation, corpus luteum formation, early embryo development and implantation.
Glucose concentration, the hexosamine biosynthesis pathway and oocyte competence.
My laboratory has been investigating the metabolic process of cumulus expansion, which involves the less well-recognized pathway of glucose metabolism, the hexosamine biosynthesis pathway, because of the belief that increased cumulus expansion related to better oocyte competence following maturation. When expansion is artificially stimulated (by addition of glucosamine) during oocyte maturation within either mouse, pig or cattle oocytes, it causes a profound inhibitory effect on oocyte competency not related to meiotic completion and only after fertilization and early cleavage had occurred. This is surprising, as this is the same pathway that must be up-regulated to provide hyaluronic acid for matrix formation. My laboratory has subsequently found that in both mouse and cow oocytes that this inhibition involves the O-linked-β-glycosylation of serines and threonines of un-identified proteins, in much the same way as kinases phosphorylate such sites on proteins
Oocyte secreted factors and oocyte competence.
With my collaborator, Rob Gilchrist, my laboratory has been studying cumulus cell – oocyte interactions and the role of oocyte secreted factors (OSFs). This has led to the discovery that the addition of native OSFs or the addition of recombinant specific factors, growth differentiation factor-9 (GDF-9) or bone morphogenetic protein-15 (BMP-15) to in vitro maturation of cattle or mouse oocytes significantly increases subsequent embryo yield by 50% and improves quality of resultant embryos and increases implantation rates post-transfer. This discovery is now patented and licensed to Cook Australia. We are pursuing this research area further and our aim is to apply this discovery to clinical IVM.
cAMP/cGMP management during oocyte maturation
As a result of ARC Linkage funding with Cook, and in a 2nd major collaboration with Rob Gilchrist, we have found that the management of cyclic adenosine monophosphate (cAMP) during IVM of either cattle or mouse oocytes, in a manner that no other laboratory has attempted, greatly increases their competence and therefore embryo yield. In cattle, the rate of blastocyst production is doubled, which is unheard of in this species. We have filed a provisional patent (filing date May 09). Our research is now directed to understand the mechanisms which cause this increase in developmental competence.
Refereed Research Publications
Clark A.R., Stokes Y.M., Thompson J.G. (2011). Estimation of glucose uptake by ovarian follicular cells. Annals of Biomedical Engineering 39: 2654-2667
Sutton-McDowall, M.L., Feil, D., Robker, R.L., Thompson, J.G., Dunning, K.R. (2012) Utilisation of endogenous fatty acid stores for energy production in bovine pre-implantation embryos. Theriogenology 77:1632-41.
Dunning, K.R., Watson, L.N., Sharkey, D.J., Brown, H.J. Norman, R.J., Thompson, J.G., Robker, R.L., Russell, D.L. (2012) Molecular filtration properties of the mouse expanded cumulus matrix: Controlled supply of metabolites and extracellular signals to cumulus cells and the oocyte. Biology of Reproduction 87: (89)1-10.
Sutton-McDowall, M.L., Mottershead, D.G., Gardner, D.K., Gilchrist, R.B., Thompson J.G. (2012) Metabolic differences in bovine cumulus oocyte complexes matured in vitro in the presence or absence of follicle stimulating hormone and bone morphogenetic protein 15. Biology of Reproduction 87: (87)1-10.
Schelbach C.J., Robker R.L., Bennett B., Gauld A.D., Thompson J.G., Kind K.L. (2013) Altered pregnancy outcomes in mice following treatment with the hyperglycaemia mimetic, glucosamine, during the periconception period. Reproduction, Fertility and Development 25: 405-416.
Kind K.L., Banwell K.M., Gebhardt K.M., Macpherson A., Gauld A., Russel D.L., Thompson J.G. (2013). Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus-oocyte complexes. Reproduction, Fertility and Development 25: 426-38.
Rose, R.D., Gilchrist, R.B., Kelly, J.M., Thompson, J.G., Sutton-McDowall, M.L. (2013) Regulation of sheep oocyte maturation using cAMP modulators. Theriogenology 79:142-148.
Frank, L.A., Sutton-McDowall, M.L., Russell, D.L, Wang, X., Feil, D.K., Gilchrist, R.B., Thompson, J.G. (2013) Effect of varying glucose and glucosamine concentration in vitro on mouse oocyte maturation and developmental competence. Reproduction, Fertility and Development 25:1095-1104.
Zeng, H., Ren, Z., Guzman, L. Wang, X., Sutton-McDowall, M.L., Ritter, L.J., De Vos, M. Smitz, J., Thompson, J.G., Gilchrist, R.B. (2013) Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence. Human Reproduction. 28: 1536-45
Gutnisky, C., Dalvit, G.C., Thompson, J.G., Cetica, P. (2013) Pentose phosphate pathway activity: Effect on in vitro maturation and oxidative status of bovine oocytes. Reproduction, Fertility and Development. RD12397.
Gutnisky, C., Morado, S., Dalvit, G. C., Thompson, J. G., Cetica, P. D. (2013). Glycolytic pathway activity: effect on IVM and oxidative metabolism of bovine oocytes. Reproduction, Fertility and Development 25: 1026-1035.
Heng, S., McDevitt, C.A., Stubing, D. B., Whittall, J. J., Thompson, J. G., Engler, T. K., Abell, A.D., Monro, T. M. (2013). Microstructured Optical Fibers and Live Cells: A Water-Soluble, Photochromic Zinc Sensor. BioMacromolecules 14: 3376-3379.
Richani, D., Ritter, L.J., Thompson, J.G., Gilchrist R.B. (2013). Mode of oocyte maturation affects EGF-like peptide function and oocyte competence. Molecular Human Reproduction 19: 500-509.
Morado, S., Cetica, P., Beconi, M., Thompson, J. G., Dalvit, G (2013). Reactive oxygen species production and redox state in parthenogenetic and sperm-mediated bovine oocyte activation. Reproduction 145: 471-478.
Caixeta, E. S., Sutton-McDowall, M. L., Gilchrist, R. B., Thompson, J. G., Price, C. A., Machado, M. F., Lima, P. F., Buratini, J. (2013). Bone morphogenetic protein 15 and fibroblast growth factor 10 enhance cumulus expansion, glucose uptake, and expression of genes in the ovulatory cascade during in vitro maturation of bovine cumulus-oocyte complexes. Reproduction 146: 27-35.
Kind, K. L., Tam, K. K. Y., Banwell, K. M., Gauld, A. D., Russell, D. R., Macpherson, A. M., Brown, H. M., Frank, L. A., Peet, D. J., Thompson, J. G. (2014). Oxygen-regulated gene expression in murine cumulus cells. Reproduction, Fertility and Development (RD13249.R1. Accepted for publication).
Richani, D., Sutton-McDowall, M.L., Frank, L.A., Gilchrist, R.B., Thompson, J.G. (2014) Effect of Epidermal Growth Factor-like peptides on the metabolism of in vitro matured mouse oocytes and cumulus cells. Biology of Reproduction (In press, Jan 16 2013/1153).
Sudiman J., Ritter, L. J., Feil, D. K., Wang, X., Chan, K., Mottershead, D. G., Robertson, D. M., Thompson, J. G., Gilchrist, R. B. (2014). Effects of differing oocyte-secreted factors during mouse in vitro maturation on subsequent embryo and fetal development. Journal of Assisted Reproduction and Genetics (Jan 11. Epub ahead of print).
Richani, D., Wang, X., Zeng, H., Smitz, J.E.J., Thompson, J.G., Gilchrist, R.B. (2014) Pre-maturation with cAMP modulators in conjunction with EGF-like peptides during IVM enhances mouse oocyte developmental competence. Molecular Reproduction and Development. (MRD-13-0300.R1 Accepted for publication)
Sugimura, S., Ritter, L. J., Sutton-McDowall, M. L., Mottershead, D. G., Thompson, J. G. and Gilchrist, R. B. (2014) Amphiregulin co-operates with bone morphogenetic protein 15 to increase bovine oocyte developmental competence: effects on gap junction-mediated metabolite supply. Molecular Human Reproduction. March 4 [Epub ahead of Print]
Frank, L. A., Sutton-McDowall, M. L., Brown, H. M., Russell, D. L., Gilchrist, R. B. and Thompson, J. G. (2014) Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of Heat shock protein 90. Human Reproduction Apr 7. [Epub]
Sutton-McDowall, M. L., Yelland, R., Macmillan, K. L., Robker, R. L. and Thompson, J. G. (2014) A study relating the composition of follicular fluid and blood plasma from individual Holstein dairy cows to the in vitro developmental competence of pooled abattoir-derived oocytes. Theriogenology Mar 18 doi: 10.1016/j.theriogenology.2014.03.011. [Epub].
Zeng, H-T, Richani, D., Sutton-McDowall, M., Ren, Z., Smitz, J.E.J, Stokes, Y., Gilchrist, R.B. and Thompson, J.G. (2014) Prematuration with cyclic adenosine monophosphate modulators alters cumulus cell and oocyte metabolism and enhances developmental competence of in vitro-matured mouse oocytes. Biology of Reproduction June 25, 2014 biolreprod.114.118471
Gilchrist R., Mottershead D., Thompson, J. (2011) Oocyte maturation and ovulation - An orchestral symphony of signalling. Australian Biochemist 42: 1-8
Smitz J.E.J., Thompson J.G., Gilchrist R.B. (2011) The promise of in vitro maturation in assisted reproduction and fertility preservation. Seminars in Reproductive Medicine 29: 24-37
Robertson S.A., Chin P.Y., Glynn D.J., Thompson J.G. (2011) Peri-conceptual cytokines - Setting the trajectory for embryo implantation, pregnancy and beyond. American Journal of Reproductive Immunology 66(Suppl. 1): 2-10.
Thompson, J.G. and Gilchrist, R.B. (2013) Pioneering contributions by Robert Edwards to oocyte in vitro maturation (IVM). Molecular Human Reproduction 19 SI: 794-798.
Frank, L.A., Sutton-McDowall, M.L., Gilchrist, R.B., Thompson, J.G. (2014) The effect of peri-conception hyperglycaemia and the involvement of the hexosamine biosynthesis pathway in mediating oocyte and embryo developmental competence. Molecular Reproduction and Development: In Press (MRD-13-0190.R1).
Thompson, J.G., Gilchrist, R.B., McDowall, M.L. (2014) Metabolism of the bovine cumulus oocyte complex revisited. Society Reproduction & Fertility Supplement. In press
Gilchrist R.B., Smitz J.E.J., Thompson J.G. (2011) Current status and future trends of the clinical practice of human oocyte in vitro maturation. In: “Human Assisted Reproductive Technology: Future Trends in Laboratory and Clinical Practice”. Gardner D.K., Rizk B.R.M.B., Falcone T. (Eds) Cambridge University Press, Leiden, the Netherlands. pp 186-198
Thompson J.G., Mottershead D.G., Gilchrist R.B. (2013) Oocyte physiology and development in domestic animals. In: “Oocyte-secreted factors in domestic animals”. Krisher R.L. (Ed). Chapter 4 pp 55-71. Wiley-Blackwell Publishing, Ames, USA.
Thompson J.G., Gilchrist R.B. (2013) Improving oocyte maturation in vitro. In: “Biology and Pathology of the Oocyte”. Trounson AO, Gosden R, Eichenlaub-Ritter U (Eds), Chapter 18, pp. 212-223. Cambridge University Press, Cambridge, UK
Robertson, S.A., Thompson, J.G. (2014) Growth factors and cytokines in embryo development. In: “Culture media, solutions, and systems in human ART.” Quinn, P. (Ed), Section 1, Chapter 9, pp 112–131. Cambridge University Press, Cambridge, UK.
Robertson, S.A., Chin, P-Y, Schjenken, J.E., Thompson, J.G. (2014) Female tract cytokines and developmental programming in embryos. In: “Cell signalling during mammalian early embryo development” Eds. D.R. Brison and H.J. Leese. [Accepted]
Simmons M, Sharpin R, Thompson J.G. (1998), USA
Patent No 5, 716, 847
(Awarded in USA, NZ and Australia). Developed into commercially manufactured and marketed product by ICPbio, Auckland New Zealand.
Product is “EmCare” embryo handling medium, sold world-wide.
Thompson J.G. (2000) NZ
Patent No 512361, Aust Patent No 761187
Internally utilized within AgResearch for the improved efficiency in the development of cloned embryos.
Gilchrist R.B., Thompson J.G., Hussein T., Dragovic R. (2005) PCT application no: PCT/AU2006/001002. National Phase in Australian, Canada, China, Europe, India, Japan, South Korea and the United States of America.
This patent protects our discovery that oocyte secreted factors, when added to in vitro maturation medium, improves the yield and quality of embryos following oocyte maturation and fertilization.
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