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Associate Professor Jeremy Thompson
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Early Development Group Members
Primary Supervisor for:
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 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
Selected publications (2005-2010) from over 100 refereed articles, reviews and book chapters published since 1980:
Sutton-McDowall ML, Gilchrist RB, Thompson JG (2010). The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction 139(4):685-95.
Schelbach C, Kind K, Lane M and Thompson JG (2010) Mechanisms contributing to the reduced developmental competence of glucosamine exposed mouse oocytes. Reproduction, Fertility and Development 22(5):771-779.
Chin PY, Macpherson AM, Thompson JG, Lane M, Robertson SA (2009). Stress response genes are suppressed in mouse preimplantation embryos by granulocyte-macrophage colony-stimulating factor (GM-CSF). Hum Reprod. 24(12):2997-3009.
Pringle KG, Kind KL, Sferruzzi-Perri AN, Thompson JG, Roberts CT (2009). Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy. Human Reproduction Update Vol 00(0):1-17.
Jansen S, Cashman K, Thompson JG, Pantaleon M, Kaye PL (2009). Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-alpha (PPARA) cause peroxisome proliferation in preimplantation mouse embryos. Reproduction. 138(3):493-505.
Irving-Rodgers HF, Morris S, Collett RA, Peura TT, Davy M, Thompson JG, Mason HD, Rodgers RJ(2009). Phenotypes of the ovarian follicular basal lamina predict developmental competence of oocytes. Hum Reprod. 24(4):936-44.
Berg D.K., Thompson J.G., Petersen, A.J. and Asher, G.W. (2008) The temporal relationship between oocyte maturation and early fertilisation events in relation to the preovulatory LH peak and preimplantation embryo development in red deer. Anim. Reprod. Sci. 105: 332-343.
Stokes, Y.M., Clark, A.R., Thompson, J.G. (2008) Mathematical modelling of glucose supply towards successful in vitro maturation of mammalian oocytes, Tiss. Eng.: Part A: 14 (9): 1539-1547.
Bakos, H.W., Thompson, J.G., Feil, D., Lane, M. (2008) Sperm DNA damage is associated with assisted reproductive technology pregnancy. Int. J. Androl. 31(5):518-26.
Wakefield, S.L., Lane, M., Schulz, S.J., Hebart, M.L., Thompson, J.G., Mitchell, M. (2008) Maternal supply of omega-3 polyunsaturated fatty acids alter mechanisms involved in oocyte and early embryo development in the mouse. Am. J. Physiol. Endocr. Metab 294:E425-34.
Tunc, O., Thompson, J.G., Tremellen, K. (2008) Development of the NBT assay as a marker of sperm oxidative stress. Int. J. Androl. [Dec 2, EPUB ahead of print]
Kimura, K., Iwata, H., Thompson, J.G. (2007) The effect of glucosamine concentration on the development and sex ratio of bovine embryos. Anim. Reprod. Sci. 103: (3,4): 228-238.
Dragovic, R.A., Ritter, L.J., Schulz, S.J., Amato, F., Thompson, J.G., Armstrong, D.T., Gilchrist, R.B. (2007) Oocyte-Secreted Factor activation of SMAD 2/3 signalling enables initiation of mouse cumulus cell expansion. Biol. Reprod. 76: 848-857.
Harvey, A.J. Navarrete Santos, A., Kirstein, M., Kind, K.L., Fischer, B. and Thompson, J.G. (2007) Differential expression of oxygen-regulated genes in bovine blastocysts. Mol. Reprod. Dev. 74 (3): 290-299. IF=2.54 (7).
Gutnisky, C., Dalvit G.C., Pintos, L.N., Thompson, J.G., Beconi, M.T. and Cetica, P.D. (2007) Influence of hyaluronic acid synthesis and cumulus mucification on bovine oocyte in vitro maturation, fertilisation and embryo development. Reproduction, Fertility and Development 19: 488-497.
Harvey A.J., Kind, K.L. and Thompson J.G. (2007) Regulation of gene expression in bovine blastocysts in response to oxygen and the iron chelator desferrioxamine. Biol. Reprod. 77: 93-101.
Pringle, K.G., Kind K.L., Thompson J.G., Roberts C.T. (2007) Complex interactions between hypoxia inducible factors, insulin-like growth factor-II and oxygen in early murine Trophoblasts. Placenta 28: 1147-1157.
Banwell K.M., Lane M., Russell D.L., Kind K.L., Thompson J.G., (2007) Oxygen concentration during mouse oocyte in vitro maturation affects embryo and fetal development. Hum. Reprod 22: 2768-2775.
Tonack S., Kind K., Thompson J.G., Wobus A.M., Fischer B., Santos A.N. (2007) Dioxin affects glucose transport via the arylhydrocarbon receptor signal cascade in pluripotent embryonic carcinoma cells. Endocrinology 148: 5902-5912.
Yeo, C.X., Gilchrist, R.B., Thompson, J.G., Lane, M. (2007). Exogenous growth differentiation factor-9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice. Hum. Reprod. 23 (1) 67-73.
Tremellen, K., Miari, G., Froiland, D., Thompson J.G. (2007) A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Aust. NZ J. Obstet. Gynaec. 47: 216-221.
Zander, D.L., Thompson, J.G. and Lane, M. (2006) Perturbations in mouse embryo development and viability caused by ammonium are more severe after exposure at the cleavage stages. Biol. Reprod. 74: 288-294.
Clark A.R., Stokes, Y.M., Lane, M. and Thompson, J.G. (2006) Mathematical modelling of oxygen concentration in bovine and murine cumulus-oocyte complexes. Reproduction 131: 999-1006.
Sutton-McDowall, M.L., Mitchell, M., Cetica, P., Dalvit, G., Pantaleon, M., Lane, M., Gilchrist, R.B. and Thompson, J.G. (2006) Glucosamine supplementation during in vitro maturation inhibits subsequent embryo development: Possible role of the hexosamine pathway as a regulator of developmental competence. Biol. Reprod. 74: 881 - 888.
Kelley, R.L., Kind, K.L., Lane, M., Robker, R.L., Thompson, J.G. and Edwards, L.J. (2006) Recombinant human follicle stimulating hormone (rhFSH) alters maternal ovarian hormone concentrations and the uterus, and perturbs fetal development in mice . Am. J. Physiol. Endocr. Metab. 291: E761-770.
Thompson, J.G. (2006) The impact of nutrition of the cumulus oocyte complex and embryo on subsequent development in ruminants. J. Reprod. Dev. 52: 169-175.
Feil, D., Lane, M., Roberts, C.T., Kelley, R.L., Edwards, L.J., Thompson, J.G. and Kind, K.L. (2006) Effect of culturing mouse embryos under different oxygen concentrations on subsequent fetal and placental development. J. Physiol. 572: 87-96.
Hussein, T.S., Thompson, J.G. and Gilchrist, R.B. (2006) Oocyte-secreted factors enhance oocyte developmental competence. Dev. Biol. 296: 514-521.
Edwards, L.J., Kind, K.L., Armstrong D.T. and Thompson, J.G. (2005) Effects of recombinant human follicle-stimulating hormone on embryo development in mice. Am. J. Physiol Endocr. Metab. 288:E845-E851.
Hussein, T., Froiland, D., Amato, F., Thompson, J.G. and Gilchrist, R.B (2005). Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J. Cell Sci. 118:5257-5268.
Sutton-McDowall, M.L., Gilchrist, R.B. and Thompson, J.G. (2005) The effect of hexoses and gonadotrophin supplementation on bovine oocyte nuclear maturation during in vitro maturation in a synthetic follicle fluid medium. Reprod. Fertil. Dev. 17:407-415.
Thompson, J.G. (2005) A mixed bag: A perspective on the regulation of IVF in Australia. Human Fertility. 8: 69-70.
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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