Associate Professor Sarah Robertson

Awards & Achievements

• Editor-in-Chief of the Journal of Reproductive Immunology (2009-ongoing)
• Chair, XI International Congress for Reproductive Immunology (2010) 
• Society for Reproductive Biology RCRH Award for excellence in reproductive biology research (2008)
• J Christian Herr Award of the American Society for Reproductive Immunology for excellence in reproductive immunology research (2005)
• Tall Poppy Award of the Australian Institute of Political Science (2000)
• Treasurer, Society for Reproductive Biology (2006-2009)
• Editorial Board member, Biology of Reproduction (2007-ongoing)
• Editorial Board member, Reproduction (2008-ongoing)  
• Board member, Bio Innovation SA (2001-ongoing)
• Advisory Board member, Mater Medical Research Institute (2008-ongoing)
• Member, NHMRC Council (2003-2006)
• Member of the Research Committee of the NHMRC (2003-2006)

Research Interests

Research in the Reproductive Immunology group centres on three related themes:

• The roles of cytokines and leukocytes in the events of embryo development during early pregnancy.
• The impact of the maternal immune response on success and quality of embryo implantation, placental development and reproductive outcome.
• Male seminal fluid signalling in the female reproductive tract and significance for reproductive events and immunity to sexually transmitted infection.

 

Research projects

 

1. Role of seminal fluid signalling in the female reproductive tract

 

We are interested in the female tract response to insemination, and hypothesise that seminal fluid is important in establishing a receptive uterine environment through activating the immune response to pregnancy.  Seminal fluid contains paternal transplantation antigens also shared by the conceptus, as well as immune-deviating cytokines that promote immune tolerance as opposed to rejection. We aim to unravel the molecular identity of the seminal signalling molecules, and characterise the nature of the cytokine and chemokine response and ensuing inflammatory events elicited in the female tissues. The physiological consequences of the female tract response for uterine receptivity, embryo development, and implantation and placental development are studied.

 

2. Uterine leukocytes and the immune response to pregnancy.

 

Antigen presenting cells (APCs) are essential for initiating immune tolerance for pregnancy and uterine immune responses to infection.  Uterine macrophages and dendritic cells are master regulators of tolerance to paternal alloantigens, through generating regulatory T cells that prevent maternal immune rejection of the conceptus.  Our current projects using T-cell transgenic models aim to investigate the cytokine regulation and role of professional and non-professional APCs in unique mechanisms for processing paternal MHC antigens at the outset of pregnancy.  Additionally, these cells have tissue remodelling functions and communicate with epithelial cells and stromal cells to impact endometrial receptivity for blastocyst implantation.  Immune-deviating cytokines including TGFb, IL-10 and IL-6 contribute to these events and their significance is being evaluated in null mutant mouse models.    

 

3.  Seminal fluid and reproductive health in women

 

In women, seminal fluid induces cellular changes and an induction of inflammatory cytokines similar to the response in mice and other animals.  The cytokine and chemokine regulation of the cervical and uterine response in women can be modelled in in vitro experiments, where we are aiming to identify the nature of the active signalling factors in human seminal fluid.  We are now seeking to investigate the influence of seminal fluid on fertility in women, and to examine the relationship between the seminal fluid content of individual signalling components and fertility status in men.  This work has implications for our understanding of the immune response to STDs such as HIV, as well as for reproductive processes. 

 

4. Role of reproductive tract cytokines in embryo development and fertility.

 

Cytokines originating from the oviduct and uterine epithelium act to regulate the development of the embryo as it traverses the reproductive tract prior to implantation.  Through effects on the timing and extent of cell proliferation and differentiation, cytokines synchronise embryo growth with the maternal changes that lead to uterine receptivity.  Our studies indicate an important role for GM-CSF in promoting optimal blastocyst development, implantation and placental development, and in programming metabolic health in offspring.  In humans, GM-CSF promotes development of healthy blastocysts and application of this discovery to improve implantation success in human IVF is now the subject of clinical trials. Our current studies are exploring the mechanisms through which GM-CSF and other maternal tract cytokines influence gene expression and developmental programming in embryos.

 

Research Funding

Our work is funded by:

 

• NHMRC Program Grant
• NHMRC Project Grant
• NHMRC Fellowship (SAR)
• ARC Discovery Grant

The Robertson lab:

 

A/Prof Sarah Robertson, PhD: NHMRC Senior Research Fellow

Wendy Ingman, PhD: Postdoctoral Scientist

Melinda Jasper, PhD: Postdoctoral Scientist

David Sharkey, PhD: Postdoctoral Scientist

Lachlan Moldenhauer, PhD: Postdoctoral Scientist

Anne Macpherson, PhD: Postdoctoral Scientist

Maria Ohlsson Teague, PhD: Postdoctoral Scientist

David Mottershead, PhD: Research Fellow

Louise Hull, MBBS, PhD: Clinical Researcher

Vicki Nisenblat, MD: Trainee Clinical Researcher

Camilla Dorian, BSc: Research Assistant

Leigh Clark, BSc: Research Assistant

Mohammed Zaheid Johan, BSc: Research Assistant

Helen Alvino: Research Nurse

Alison Care, BSc: PhD student

Leigh Guerin, BSc: PhD student

Peck-Yin Chin (Loretta), BSc; PhD student

Leanne Srpek: Lab Manager Admin Assistant

 

 

Publications

Selected publications (2004-2009) from 90 refereed articles, reviews and book chapters published since 1990:

 

Moldenhauer LM, Diener KR, Brown MP, Hayball JD, Robertson SA (2009) Cross-presentation of male seminal fluid antigens elicits T cell activation to initiate the female immune response to pregnancy. Journal of Immunology (in press)

 

Guerin L, Prins J, Robertson SA (2009) T regulatory cells and immune tolerance in pregnancy – a new target for infertility treatment?  Human Reproduction Update (epub ahead of print)

 

Sferruzzi-Perri AN, Macpherson AM, Roberts CT, Robertson SA  (2009) Csf2 null mutation alters placental gene expression and trophoblast glycogen cell and giant cell differentiation in mice. Biology of Reproduction (epub ahead of print)

 

Robertson SA, Guerin LR, Bromfield JJ, Branson KM, Ahlström AC, Care AS (2009) Seminal fluid drives expansion of the CD4⁺CD25⁺ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biology of Reproduction (epub ahead of print)

 

Ohlsson Teague EMC, Van der Hoek KH, Van der Hoek MB, Perry N, Wagaarachchi P, Robertson SA, Print CG, Hull ML (2009) MicroRNA-regulated pathways associated with endometriosis. Molecular Endocinology 23: 265-275

 

O’Leary S, Lloyd M, Shellam GR, Robertson SA (2008). Immunization with recombinant murine cytomegalovirus expressing murine zona pellucida 3 causes permanent infertility in BALB/c mice due to follicle depletion and ovulation failure. Biology of Reproduction 79: 849-860

 

Ingman WI, Robertson SA (2008) The effect of TGFb1 null mutation on mammary gland development in mice – systemic and epithelial effects. Biology of Reproduction 79: 711-717

 

Robertson SA (2007) GM-CSF regulation of embryo development and pregnancy Cytokine and Growth Factor Reviews 18: 287-298

 

Ingman WI, Robertson SA (2007) TGFb1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction. Endocrinology 148(8): 4032-4043

 

Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA (2007) Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells.  Molecular Human Reproduction 13: 491-501

 

Jasper MJ, Tremellen KP and Robertson SA (2007) Reduced endometrial IL-6 expression in recurrent miscarriage. Journal of Reproductive Immunology 73: 74-84.

 

Robertson SA, Skinner RJ, Care AS (2007) Interleukin-10 regulates inflammatory cytokine synthesis to protect against LPS-induced abortion and fetal growth restriction in mice. Biology of Reproduction 76:738-48.

 

Ingman WI, Robker RL, Woittiez K, Robertson SA (2006) Null mutation in TGFb1 disrupts ovarian function causing impaired folliculogenesis, oocyte incompetence and early embryo arrest. Endocrinology 147: 835-45.

 

Jasper MJ, Tremellen KP and Robertson SA (2006) Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Molecular Human Reproduction 12: 301-8.

 

O’Leary S, Jasper MJ, Robertson SA and Armstrong DT (2006) Seminal plasma regulates ovarian progesterone production, leukocyte recruitment and follicular cell responses in the pig. Reproduction 132: 147-58.

 

Robertson SA, Care AS, Skinner RJ (2006) Essential role for interleukin-10 in resistance to LPS-induced preterm labour in mice. Journal of Immunology 177: 4888-96.

 

Sjoblom C, Roberts CT, Wikland M, Robertson SA (2005) GM-CSF alleviates adverse consequences of embryo culture on placental morphogenesis and fetal growth.  Endocrinology 146: 2142-53.

 

Robertson SA (2005) Seminal plasma and male factor signalling in the female reproductive tract.  Cell and Tissue Research 322:43-52.

 

White CA, Johansson M, Roberts CT, Ramsay AJ, Robertson SA (2004) Effect of interleukin-10 null mutation on maternal immune response and reproductive outcome in mice. Biology of Reproduction 70:123-31

 

Hudson Keenihan SN, Robertson SA. (2004) Diversity in phenotype and steroid hormone dependence in dendritic cells and macrophages in the mouse uterus.  Biology of Reproduction 70: 1562-1572

 

Johansson M, Bromfield JJ, Jasper MJ, Robertson SA. (2004) Semen activates the female immune response during early pregnancy in mice.  Immunology 112: 290-300.

 

O'Leary S, Jasper MJ, Warnes GM, Armstrong DT and Robertson SA (2004) Seminal plasma regulation of endometrial cytokine expression and leukocyte recruitment in the pig. Reproduction 128: 237-47.

 

Patents

 

Robertson SA and Tremellen KP (1998), Luminis Pty Ltd (owner). IPN WO 98/39021 “Treatment and diagnosis of infertility using TGFß”. International Publication Date 11 September 1998. Claiming priority from PO5508 dated 6 March 1997.

 

Robertson SA, Sjöblom C and Wikland MF (1999), Luminis Pty Ltd and Fertilitetscentrum AB (co-owners) IPN WO 99/67364 “Method and medium for in vitro culture of human embryos”. International Publication Date 29 December 1999.  Claiming priority from PP4212 dated 19 June 1998.

 

Robertson SA, Sharkey D, Glynn D and Tremellen KP (2003), University of Adelaide (owner). IPN WO 2004/026333 “Treatment and diagnosis of an infertility condition by measuring or inhibiting interferong” filed 20 Sept 2003, International Publication Date 1 April 2004.  Claiming priority from PP2002951531 filed 20 Sept 2002.

 

Expertise for Media Contact

Categories	Fertility & reproduction
Expertise	reproductive biology and function; infertility (implantation failure, recurrent spontaneous abortion, uterine receptivity); embryo (in vitro culture, growth factors, IVF); Pregnancy (immunology of pregnancy, early pregnancy, embryo implantation, insemination and pregnancy, animal models)
Notes	Alt phone: (08) 8303 5100

Entry last updated: Sunday, 22 Nov 2009