Associate Professor Rebecca Robker
|Org Unit||Paediatrics and Reproductive Health|
|Telephone||+61 8 8313 8159|
Adelaide Health and Medical Sciences Building
I am currently accepting postgraduate students to work on a number of exciting projects relating to nutritional control of oocyte quality and molecular mechanisms of ovulation. Please contact me if you are interested to interview.
Cellular mechanisms that control ovarian function.
All aspects of women's health are dependent upon proper functioning of the ovary, which produces essential steroid hormones as well as oocytes- precious cells which are the foundation for transmission of life. The ovarian follicle consists of multiple cell types with highly specialized functions co-ordinated to establish a growth-promoting microenvironment that determines the ability of an oocyte to form an embryo- its developmental competence. Understanding the follicular microenvironment, how it is established and how it maintains oocytes and regulates their differentiation and successful release (ovulation) for fertilization is essential for modulating fertility and optimizing healthy development.
My research aims to improve reproductive health in women by identifying cellular pathways in the ovary that regulate oocyte quality and ovulation, particularly those incorporating maternal hormone, immunological and metabolic inputs.
1. Identifying the molecular mechanisms that control ovulation.
The molecular mechanisms that control ovulation are not known, even though hormone-based contraceptive pills are used by 100 million women worldwide to prevent oocyte release and anovulation is a major cause of human infertility. My laboratory has contributed key discoveries in dissecting the cellular mechanisms by which the oocyte is released from the ovarian follicle into the oviduct for fertilisation. Specifically we have found that the progesterone receptor transcription factor and the protease Adamts-1 are essential for ovulation. We now use genetically modified mouse models and microarray analyses to identify novel gene products that are the mediators of the dynamic tissue remodelling processes that facilitate the release of the oocyte. Identifying mechanisms underlying the fundamental process of ovulation affords the opportunity to develop strategies for understanding and preserving normal female fertility, as well as to identify potential new therapies for anovulation and ectopic pregnancy.
2. Determining why maternal obesity and Polycystic Ovary Syndrome (PCOS) impair ovulation and diminish oocyte developmental competence.
The earliest foundations of embryo growth potential are established by peri-conception metabolic and nutritional signals to the oocyte from the mother. My laboratory has found that diet-induced obesity in female mice results in impaired ovulation and decreased oocyte developmental competence. This effect is strongly associated, in both mice and humans, with alterations in the follicular microenvironment, particularly lipid metabolism and lipid-induced stress pathways. We are now identifying interventions in vitro and in vivo that can normalise these cellular defects and improve embryo outcomes. This will enable us to determine how metabolic syndromes in women, such as obesity and PCOS, impact ovarian function and early embryo development; and thus how our modern diet and the consequent obesity epidemic contributes to rising female infertility.
3. Investigating how immune cells influence ovarian function.
Immune cells, a major source of cytokines, are prevalent in the ovary, localize in a distinct manner to specific follicle types, and are considered to be important regulators of ovarian function. There is little definitive data however on the cellular and molecular mechanisms by which immune cells interact with ovarian cells and modulate normal ovarian function. Using genetically modified mouse models we are able to track immune cells, including macrophages, neutrophils and T cells, in the ovary and closely monitor their localisation and activation status. Further, using mice lacking important immune cell receptors, we are able to identify cellular mechanisms by which immune cells directly influence events in the ovary. For instance we have used ICAM-1 null mice to demonstrate that ICAM-1, a cellular adhesion receptor that tethers leukocytes and initiates their migration into tissues, is involved in ovulation and luteal regression, essential tissue remodelling events in the ovary.
Wu LL, Russell
DL, Wong SL, Chen M, Tsai TS, St. John J, Norman RJ, Febbraio MA, Carroll J, Robker
Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors
Development 2015 Feb 15;142(4):681-91.
Lane M, Robker
RL, Robertson SA.
Parenting from before conception.
Science. 2014 Aug 15;345(6198):756-60.
Turner N, Robker RL
Developmental programming of obesity and insulin resistance: does mitochondrial dysfunction in oocytes play a role?
Molecular Human Reproduction 2015 Jan;21(1):23-30
Dunning K, Russell DL, Robker RL.
Lipids and oocyte developmental competence: the role of fatty acids and B-oxidation.
Reproduction. 2014 148(1):R15-27
Boden MJ, Kennaway DJ, Russell DL, Robker RL
Progesterone receptor (PGR) dependent regulation of genes in the oviducts of female mice
Physiological Genomics 2014 Aug 15;46(16):583-92
Chen M, Wu L, Zhao J, Wu F, Davies MJ, Wittert GA,
Norman RJ, Robker RL, Heilbronn
Altered glucose metabolism in mouse and humans conceived by in-vitro fertilization (IVF).
Diabetes. 2014 Oct;63(10):3189-98
Yang X, Wu LL, Chura LR, Liang X, Lane M, Norman RJ, Robker
Exposure to lipid-rich follicular fluid is associated with endoplasmic reticulum stress and impaired oocyte maturation in cumulus-oocyte complexes
Fertility and Sterility DOI: 10.1016/j.fertnstert.2012.02.034
Wu LL, Russell DL, Norman RJ, Robker RL
Endoplasmic Reticulum (ER) Stress in Cumulus-Oocyte Complexes Impairs Pentraxin-3 Secretion, Mitochondrial Membrane Potential (ΔΨm), and Embryo Development.
Molecular Endocrinology 2012 Apr;26(4):562-73.
Akison LK, Alvino ER, Dunning KR, Robker RL, Russell DL
Transient Invasive Migration in Mouse Cumulus Oocyte Complexes Induced at Ovulation by Luteinizing Hormone
Biology of Reproduction. 2012 Apr 27;86(4):125.
Dunning KR, Akison LK, Russell DL, Norman RJ, Robker RL
Increased beta-oxidation and improve oocyte developmental competence in response to L-carnitine during ovarian in vitro follicle development in mice.
Biology of Reproduction. 2011 Sep;85(3):548-55.
Wu LL-Y, Dunning KR, Yang X, Russell DL, Lane M, Norman
RJ, Robker RL
High fat diet causes lipotoxicity responses in cumulus-oocyte-complexes and decreased fertilization rates
Endocrinology. 2010 Nov;151(11):5438-45.
Dunning KR, Cashman K, Russell DL, Thompson JG, Norman
RJ, Robker RL
Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development
Biology of Reproduction. 2010 Dec;83(6):909-18.
Yang X, Dunning KR, Wu LL-Y, Hickey TE,
Norman RJ, Russell DL, Liang X, Robker RL
Identification of Perilipin-2 as a lipid droplet protein regulated in oocytes during maturation
Reproduction Fertility and Development. 2010;22(8):1262-71.
RL, Akison LK, Bennett BD, Thrupp PN, Chura LR, Russell DL, Lane M, Norman RJ.
Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared to Moderate Weight Women.
J Clin Endocrinol Metab. 2009 May;94(5):1533-40.
Robker RL, Akison LK, Russell DL
Control of oocyte release by progesterone receptor-regulated gene expression.
Nucl Recept Signal. 2009 Dec 31;7:e012.
CE, Bennett BD, Norman RJ, Robker RL.
Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.
Endocrinology. 2008 May;149(5):2646-56.
Evidence that obesity alters the quality of oocytes and embryos.
Pathophysiology. 2008 Aug;15(2):115-21.
Russell DL, Robker RL
Molecular Mechanisms of Ovulation: Co-ordination through the cumulus complex.
Human Reproduction Update. 2007 May-Jun;13(3):289-312.
Wu R, Ryan
NK, Van der Hoek KH, Jasper MJ, Sini I, Robertson SA, Robker RL, Norman RJ.
Ovarian leukocyte distribution and cytokine/chemokine mRNA expression in follicular fluid cells in women with polycystic ovary syndrome.
Human Reproduction. 2007 Feb;22(2):527-35.
DK, Smith EO, Mersmann H, Smith CW, Robker RL.
ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice.
American Journal of Physiology- Cell Physiology. 2006 Dec;291(6):C1232-9.
Ingman WV, Robker RL, Woittiez K, Robertson SA.
Null mutation in transforming growth factor beta1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest.
Endocrinology. 2006 Feb;147(2):835-45.
Ryan NK, Van Der Hoek KH, Robker RL, Norman RJ.
Troglitazone regulates peroxisome proliferator-activated receptors and inducible nitric oxide synthase in murine ovarian macrophages.
Biology of Reproduction. 2006 Jan;74(1):153-60.
23. Robker RL, Collins RG, Beaudet AL,
Mersmann HJ Smith CW.
Leukocyte migration in adipose tissue of mice null for ICAM-1 and Mac-1 adhesion receptors.
Obesity Research. 2004 Jun;12(6):936-40.
Wu R, Van
der Hoek KH, Ryan NK, Norman RJ, Robker
Macrophage contributions to ovarian function.
Human Reproduction Update. 2004 10(2):119-33.
Russell DL, Espey LL, Lydon JP, O’Malley BW, Richards JS. Progesterone-regulated genes in the ovulation
process: ADAMTS-1 and cathepsin L proteases.
Proceedings of the National Academy of Sciences of the USA (PNAS). 2000 97(9):4689-94.
Hormone- induced proliferation and differentiation of granulosa cells: a coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1.
Molecular Endocrinology. 1998 12(7):924-40.
Richards JS. Hormonal control of
the cell cycle in ovarian cells: proliferation versus differentiation.
Biology of Reproduction. 1998 59(3):476-82.
Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner
H, Park MY, Robker RL, Richards
JS, McGinnis LK, Biggers JD, Eppig JJ, Bronson RT, Elledge SJ, Weinberg
Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.
Nature. 1996 384(6608):470-4.
To link to this page, please use the following URL: http://www.adelaide.edu.au/directory/rebecca.robker