A Healthy Start to Life: Pregnancy Research
See full list of projectsPre-eclampsia: women’s perceptions of their experience
Supervisors: Dr Christine East, Prof Shaun Brennecke
Location: Department of Obstetrics & Gynaecology, Royal Women’s Hospital, University of Melbourne
Contact: 8345 3718 Email: eastc@unimelb.edu.au
This project seeks to consider women’s experiences of pre-eclampsia, a condition associated with elevated blood pressure, proteinuria, seizures (eclampsia) and potentially substantial morbidity for mother and baby, in the later half of pregnancy. The only known cure is delivery of the baby and placenta. Women often approach pregnancy with no expectation of the potential severity of this disorder and may be faced with deteriorating health and urgent interventions that can have serious short- and long-term medical and psychological effects. A major focus of this project will be women’s experiences with severe pre-eclampsia or eclampsia, particularly how much prior knowledge they had of its potential emergence and how they felt during the process of diagnosis and progression of illness to birthing and beyond.
Skill acquisition: Quantitative and qualitative survey and interview techniques and analysis.
Ambulatory fetal activity monitoring
Supervisor: Dr Christine East
Location: Department of Obstetrics & Gynaecology, Royal Women’s Hospital, University of Melbourne
Contact: 8345 3718 Email: eastc@unimelb.edu.au
This project considers the movements of healthy and compromised fetuses. Many women become concerned about their unborn baby’s movements during pregnancy and it is well established that compromised babies move less than healthy babies. In this project we record fetal movements using an Ambulatory Fetal Activity Monitor, which uses accelerometers that detect motion (like those in an iPhone or Nintendo Wii). The project will focus on what is normal fetal movement, a unique potential generated by this project, as no similar technology has previously been available to record fetal activity during normal and/or prolonged maternal activity. A further focus will be movement in the compromised fetus.
Skill acquisition: Research data acquisition, including clinical content, quantitative and comparative analysis. Signal processing (engineering) may also be considered.
Role of proteoglycans in preventing thrombosis within the human placenta
Supervisors: Dr Joanne Said and Dr Gayathri Rajaraman
Location: Pregnancy Research Centre, The Royal Women’s Hospital
Contact: Dr Joanne Said T: 8345 3717 E: jsaid@unimelb.edu.au, Dr Gayathri Rajaraman T: 8345 3753 E: graja@unimelb.edu.au
Fetal growth restriction (FGR) is a serious pregnancy complication with significant short and long term sequelae. The aetiology remains largely idiopathic, although thrombosis within the placental circulation is a frequent finding. Proteoglycans and their glycosaminoglycan (GAG) side chains display important anticoagulant properties and our recent work supports a possible association between reduced expression of these macromolecules and FGR. This study aims to investigate the differences in GAG activity within the placentae of women whose pregnancies have been complicated by FGR and those who experience uncomplicated pregnancies. If our hypothesis is confirmed, there will be the potential to develop appropriate therapeutic strategies (such as anticoagulants) which may help to prevent the development of thrombosis and thus the complications of FGR. Given the serious life-long consequences of this complication, such intervention strategies would be regarded as well worthwhile.
Techniques: Human placental tissue collection, GAG isolation and characterisation by high performance liquid chromatography (HPLC), anticoagulant activity assays.
Mesenchymal stem cell and vascular endothelial cell interactions in the placental bed in human pregnancy
Supervisors: Dr Neil Gude and Dr Bill Kalionis
Location: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Neil Gude T: 8345 3751 E: neil.gude@thewomens.org.au, Dr Bill Kalionis T : 8345 3748 E: bill.kalionis@thewomens.org.au
A healthy pregnancy is dependent on successful remodelling of the uterine blood vessels at the site of placental formation. This process involves replacement of maternal vascular cells with placental trophoblast cells and results in reduction in vascular resistance and increased maternal blood flow to the growing placenta. The common, serious pregnancy disorders of pre-eclampsia and fetal growth restriction have significant adverse effects on the health and well-being of mothers and their babies. During these disorders uterine blood vessel remodelling and placental perfusion is deficient. The aim of this project is to elucidate the role of mesenchymal stem cell and vascular endothelial cell interactions in the processes of uterine vascular remodelling. It is proposed that a critical role of uterine mesenchymal stem cells is to regulate the changing functions of endothelial cells during early pregnancy. It is further proposed that this important regulatory interaction is disturbed during pregnancy disorders.
Techniques: human cell isolation and culture, whole cell functional assays, PCR-based analysis, immunocytochemical analysis, Western blotting and ELISA
Stem cells of Reproductive Tissues: their biology and potential in regenerative medicine
Supervisor: Dr Bill Kalionis and Dr Rishika Pace
Location: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Bill Kalionis T : 8345 3748 E: bill.kalionis@thewomens.org.au, Dr Rishika Pace E: rapace@unimelb.edu.au
Stem cells are precursor cells with the ability to differentiate into a variety of different cell types. Typically, stem cells are categorized into “embryonic” (which arise from embryos and have the capacity to give rise to all cell types) and “adult” (which are undifferentiated cells found amongst differentiated cells in a tissue or organ and give rise to a more restricted range of cells.). Stem cells are being used in clinical trials for regeneration and repair of bone and other tissues and even for the treatment of cancers. The placenta is a rich source of stem cells with advantages over other sources of cells. Our understanding of the biology of stem cells in the placenta is still at a rudimentary stage. The project will involve gene expression and functional analysis of a gene that is important in placental stem cells.
Techniques: stem cell preparation and characterisation by immunocytochemistry and FACS, RNA/DNA extraction methods, real-time PCR, siRNA and gene overexpression analysis and immunohistochemistry. Functional analyses will include proliferation, migration and differentiation assays.
How do chemokines affect fetal trophoblast adhesion?
Supervisor: Dr Rosemary Keogh
Location: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Rosemary Keogh E: rosemary.keogh@thewomens.org.au
Late in the first trimester of human pregnancy, cells known as trophoblast migrate from the placenta and invade the arteries of the uterine wall. As they invade, the trophoblast interact with the vessels and instigate remodelling of the vessel walls. The end result is that the arteries are transformed from narrow to wide bore vessels thus facilitating blood flow to, and from, the placenta. This is an essential process to enable the fetus to develop and grow normally. In pregnancies where this remodelling is compromised, complications can arise such as pre-eclampsia, leading to poor outcomes for both the mother and baby. This project will investigate how trophoblast cells are able to migrate into maternal vessels by examining their ability to adhere to the blood vessel wall and components of the extracellular matrix. In particular, the effect of chemokines, a subgroup of cytokines, on trophoblast adhesion will be studied. The specific objectives will be to determine 1) the matrix composition surrounding the uterine arteries, 2) the effect of chemokines on trophoblast adhesion to matrix components and 3) the effect of chemokines on trophoblast adhesion to endothelial cells.
Techniques: tissue culture, western blotting, adhesion assays, immunofluorescence and confocal microscopy.
Do the aminopeptidases ARTS-1 and LNPEP regulate trophoblast functions?
Supervisor: Dr Rosemary Keogh
Location: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Rosemary Keogh E: rosemary.keogh@thewomens.org.au
Pre-eclampsia is a common and serious disorder of human pregnancy that is associated with serious health issues for both the mother and baby. It is characterized by the onset of maternal hypertension in the latter half of pregnancy. However, the pathogenesis of pre-eclampsia is not known. In a normal pregnancy, cells known as trophoblast invade the arteries in the uterine wall and replace the endothelial and smooth muscle cells. This dilates the arteries and facilitates an increase in blood flow to the placenta to allow the fetus to grow and develop. In pre-eclamptic pregnancies, this invasion is limited with consequent reduced remodelling of the arteries and a restriction of maternal placental blood flow.
Genetic analysis has identified candidate genes that encode animopeptidase enzymes that may be involved in the development of pre-eclampsia. The aim of this project is to characterize the function of these aminopeptidases (ARTS-1 and LNPEP) in regulating trophoblast cell functions. The specific objectives will be to determine 1) the localization of ARTS-1 and LNPEP in trophoblast cells, 2) if ARTS-1 and LNPEP regulate trophoblast migration and invasion and 3) if ARTS-1 and LNPEP regulate trophoblast survival.
Techniques: tissue culture, RNAi, western blotting, immunofluorescence and migration and proliferation assays.
Regulation of pregnancy hormone chorionic gonadotropins in human pregnancy disorders
Supervisors: Dr Padma Murthi and Dr Niro Pathirage
Location: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Padma Murthi E: padma@unimelb.edu.au, Dr Niro Pathirage E: npa@unimelb.edu.au
A critical step in establishment of human pregnancy is the invasion of the uterus wall by extravillous cytotrophoblasts (EVCT) during the first trimester. It is well established that human chorionic gonadotropin (hCG) is secreted by the endocrine syncytiotrophoblast (ST) into the maternal compartment. We have preliminary studies to show that invasive EVCT also produce hCG, suggesting a possible role in the modulation of trophoblast invasion. This project will investigate the role of transcription factors in the regulation of hCG in normal placental development and in disorders of pregnancy such as fetal growth restriction and pre-eclampsia.
Techniques: cell and molecular biology, immunoblotting, immunohistochemistry, functional assays including proliferation, migration and invasion.
Identification of factors that regulate placental angiogenesis
Supervisors: Dr Padma Murthi, Dr Niro Pathirage and Dr Rosemary Keogh
Location: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Padma Murthi E: padma@unimelb.edu.au, Dr Rosemary Keogh E: rosemary.keogh@thewomens.org.au
Angiogenesis or new blood vessel formation is co-ordinated by placental trophoblast cells and endothelial cells. Aberrant placental angiogenesis is associated with complications of pregnancy disorders such as fetal growth restriction and pre-eclampsia. This project will identify factors that are released by trophoblast cells on endothelial cell function such as proliferation, migration and network formation.
Techniques: cell and molecular biology, immunoblotting and immunohistochemistry.