The placenta

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Vascular remodelling during pregnancy

Dr Rosemary Keogh, Prof Shaun Brennecke

Pre-eclampsia is a major cause of maternal morbidity and mortality in both Western and developing countries affecting some 2-10% of all pregnancies. It is also a major contributing factor to perinatal death, fetal growth restriction and preterm birth. Furthermore, there is now evidence that women who have pre-clampsia have a greater risk of developing cardiovascular disease later in life. Despite this, our understanding of the underlying causes of these pregnancy complications is limited.

The development of pre-eclampsia, fetal growth restriction and the early onset of labour have all been associated with shallow placental trophoblast invasion and incomplete remodelling of maternal uterine arteries. Late in the first trimester of human pregnancy, trophoblast cells migrate from the placenta and invade the arteries of the uterine wall. As they invade they interact with the vessels and instigate remodelling of the vessel walls. This results in transformation of the arteries from narrow to wide bore vessels thus facilitating blood flow to the placenta. This essential process enables the fetus to develop and grow normally. When the process is compromised, pregnancy complications develop.

The aims of this project are to determine 1) factors that regulate trophoblast invasion into uterine arteries, 2) the effect of factors identified in Aim 1 on trophoblast function (migration, invasion, adhesion) and 3) if either the factors identified in Aim 1 or their effects identified in Aim 2 are altered in compromised pregnancies.

Factors influencing the growth of the placenta into the uterus

Dr Maria Kokkinos, Prof Shaun Brennecke

In order for the healthy development of the fetus it is important that the placenta is growing well in the mother’s uterus.

Two very important pregnancy diseases, pre-eclampsia (PE) and fetal growth restriction (FGR) can be caused by reduced growth of the placenta. Pre-eclampsia, is identified in up to 8% of pregnancies and plays a major role in complications and mortality in the mother and baby. In the 3-5% of pregnancies affected by FGR, 70% will be the result of an abnormal growth of the placenta. In both of these pregnancy disorders, the growth and health of the baby is affected, and there can be serious implications on the health of the mother. By determining what factors are involved in the healthy growth of the placenta we may be able to use these factors to improve the assessment and treatment of these disorders.

We plan to study the growth of placentae in normal compared to FGR and pre-eclampsia diagnosed pregnancies, so that we may help to unravel mechanisms involved in the establishment, and continued development, of healthy pregnancies, which may lead to improved early detection methods for these very significant illnesses.

Understanding the contribution to adverse pregnancy outcomes of thrombosis in the maternal and fetal circulations of the human placenta

Dr Joanne Said, Dr Padma Murthi, Dr Amy Chui, Dr Vera Ignjatovic, Prof Paul Monagle, Prof Shaun Brennecke

In normal pregnancy, blood flow through the maternal and fetal circulations of the placenta is well maintained, with little or no blood clotting (thrombosis) occurring because the placenta contains naturally occurring anticoagulant substances. These contribute to the healthy functioning of the placenta and help ensure an appropriate supply of oxygen and nutrition passes through the placenta from the mother to the growing fetus. However, in a number of adverse pregnancy outcomes, including pre-eclampsia, fetal growth restriction, placental abruption and fetal death in utero, blood clots within the placenta are a feature. This suggests that blood clotting in the maternal and fetal circulations of the placenta may be contributing to these disorders. In this study, we intend to explore the hypothesis that abnormalities of anticoagulation pathways within the placental circulations contribute to the pathogenesis of these conditions. To this end, we propose investigating the molecular and functional mechanisms regulating thrombosis in the placental circulations in both normal pregnancies and those complicated by these pathologies.

TIPPS: Thrombophilia in Pregnancy Prophylaxis Study

Dr Joanne Said, Ms Di Maxwell and Ms Megan Poth
Local co-ordinators of the multi-centre TIPPS trial, which is based at the Ottawa Hospital Research Institute in Canada and led by the chief investigator Dr Marc Rodger

The TIPPS trial seeks to determine the safety and effectiveness of low-molecular-weight heparin (LMWH), an anticoagulant, in preventing placenta mediated pregnancy complications and venous thromboembolism (VTE) in women with thrombophilia. Thus, the principal research question is: can LMWH prevent thrombosis in the leg veins, pulmonary arteries and placental vessels, thereby reducing the risk of deep vein thrombosis, pulmonary embolism, intrauterine growth restriction (IUGR), preeclampsia, miscarriage and stillbirth?

Early diagnosis of common pregnancy disorders

Dr Neil Gude, Ms Janet Stevenson, Ms Kimberley Crawford, Dr Bill Kalionis, Prof Shaun Brennecke

There is an important need in modern obstetric care for non-invasive blood-based tests for the accurate assessment of the risks early in pregnancy that patients will develop common pregnancy disorders. The aim of this project is to develop these types of tests for the pregnancy disorders pre-term labour, pregnancy-induced hypertension/pre-eclampsia, fetal growth restriction and gestational diabetes. Although these diseases affect between 15 and 25% of deliveries in Australia and have a significant impact on the health and wellbeing of mothers and their babies, diagnosis is made in the clinic only after they are well established. Available predictive tests provide relatively poor estimations of risks. The placenta plays a critical pathogenic role in the pregnancy disorders and altered placental protein expression and release into maternal blood are important features of the disease process in each case.

This project uses a proteomics approach to identify candidate placental proteins that may be suitable for development as predictive tests. Evaluation of the predictive/early diagnostic capacity of the protein biomarkers is made by measuring their concentrations in maternal blood prior to clinical manifestation of disease.

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