Senior Research Fellow
Research interestsResearch 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 and reproductive outcome.
- Male seminal fluid signalling in the female reproductive tract and significance for reproductive events and immunity to sexually transmitted infection.
- 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.
- Uterine leukocytes and the immune response to pregnancy
Antigen processing and presentation by antigen presenting cells (APCs) in co-ordinating uterine immune responses is an additional focus. Critically, uterine macrophages and dendritic cells are implicated in driving tolerance to paternal alloantigens, including generation of novel populations of endometrial and decidual regulatory T cells important for embryo implantation. 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 and in regulating endometrial receptivity for blastocyst implantation. Immune-deviating cytokines including TGF b , IL-10 and IL-6 contribute to these events and their significance is being evaluated in null mutant mouse models.
- Seminal plasma elicits immunological changes in the human cervix
In collaboration with colleagues at the Karolinska Institute, Stockholm , we have demonstrated that cellular changes and an induction of inflammatory cytokines similar to the response described in mouse and pig, also take place in the cervix of women after intercourse. The cytokine and chemokine regulation of this cervical response 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 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.
- 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 in mice indicate an important role for GM-CSF in promoting optimal blastocyst development, implantation and placental development, and in programming metabolic health in offspring. A critical role for GM-CSF in development of human blastocysts has also been demonstrated, and application of this discovery to improve implantation success in human IVF is now the subject of clinical trials.
Staff and students
|Prof Sarah Robertson||NHMRC Senior Research Fellow|
|Leanne Srpek||Administration Assistant / Lab Manager|
|Dr Melinda Jasper||NHMRC Research Associate|
|Dr Wendy Ingman||NHMRC CJ Martin fellow|
|Dr David Sharkey||NHMRC Research Associate|
|Dr Anne Macpherson||NIH Research Associate|
|Dr Hitomi Nakamura||Serono Foundation Fellow|
|Sean O'Leary||ARC Research Associate|
|Lachlan Moldenhauer||PhD candidate|
|Leigh Guerin||PhD candidate|
|Alison Care||PhD candidate|
Our work is funded by:
- NHMRC Program Grant
- ARC Discovery Grant
- NHMRC Development Grant
- NHMRC Project Grant
- NIH Grant
Selected Recent Publications and Patents
Robertson SA (2007) GM-CSF regulation of embryo development and pregnancy Cytokine and Growth Factor Reviews (in press)
Ingman WI, Robertson SA (2007) TGF b 1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunstion E ndocrinology (in press)
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 (in press)
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 TGF b 1 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.
Robertson SA , Roberts CT, van Beijering E , Pensa K, Sheng Y, Shi T, Krilis SA. (2004) Effect of b 2 -glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody mediated pregnancy pathology in mice. Molecular Human Reproduction 10: 409-16.
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 .
Sjöblom C, Wikland M, Robertson SA . (2002) GM-CSF acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos. Biology of Reproduction 67:1817-1823.
Ingman WV and Robertson SA (2002) Defining the actions of transforming growth factor beta in reproduction. Bioessays 24, 904-914.
Robertson SA and Sharkey D (2001) The immunological significance of semen and insemination. Seminars in Immunology 13:243-254.
Robertson SA , Sjöblom C, Jasper MJ, Norman RJ, Seamark RF (2001) Granulocyte-macrophage colony-stimulating factor promotes glucose transport and blastomere viability in murine pre-implantation embroys. Biology of Reproduction 64:1206-1215.
Sheng YS, Reddel SW, Herzog H, Wang YX, Brighton T, France MP, Robertson SA , Krilis SA (2001) Impaired thrombin generation in ß2-glycoprotein I (ß2GPI) null mice. Journal of Biological Chemistry 276:13817-13821.
Tremellen KP, Valbuena D, Landeras J, Ballesteros A, Martinez J, Mendoza S, Norman RJ, Robertson SA , Simon C (2000) The effect of intercourse on pregnancy rates during assisted human reproduction. Human Reproduction 15:2653-2658.
Robertson SA (2000) Control of the immunological environment of the uterus. Reviews in Reproduction 5:164-174.
Robertson SA and Tremellen KP (inventors), University of Adelaide IPN WO 98/39021 "Treatment and diagnosis of infertility using TGFbeta". International Publication Date 11 September 1998. Filed in Australia , US, Europe and Canada . Claiming priority from PO5508 dated 6 March 1997.
Robertson SA, Sjöblom C and Wikland MF (inventors), University of Adelaide 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. Filed in Australia , US, Europe and Canada . Claiming priority from PP4212 dated 19 June 1998.
Robertson SA, Sharkey D and Tremellen KP (inventors), University of Adelaide . "Treatment and diagnosis of an infertility condition by measuring or inhibiting interferon-gamma". Provisional specification lodged 20 September 2002.