Current projects

Below is a selection of current and recent research projects involving members of the Early Origins of Adult Health Research Group.

Is there a link between birth weight and the risk of left ventricular hypertrophy?

The small fetus has fewer cardiomyocytes than the normally grown fetus and thus these fewer cardiomyocytes must get bigger to maintain heart growth. Left ventricular hypertrophy is a risk factor for cardiovascular disease and these small babies are also at increased risk of cardiovascular disease in adult life. We will perform a systematic review to determine when left ventricular hypertrophy becomes apparent in children and adults who were born small.

A/Prof Janna Morrison and A/Prof Marie Williams 

Is resveratrol beneficial during pregnancy?

 

Does metformin in the periconceptional period increase fetal growth?

 

Can a periconceptional intervention normalise blood pressure regulation in pregnancies at risk of IUGR?

The small fetus has fewer cardiomyocytes than the normally grown fetus and thus these fewer cardiomyocytes must get bigger to maintain heart growth. These small babies are also at increased risk of cardiovascular disease in adult life. We speculate that stimulating proliferation of cardiomyocytes in the small fetus may normalise cardiomyocytes number in the heart and prevent hypertrophy from occurring. Left ventricular hypertrophy is a risk factor for cardiovascular disease. We will isolate cardiomyocytes from the heart of sheep fetuses and culture them. They will be treated with drugs that can cause proliferation of rat cardiomyocytes. The number of cardiomyocytes compared to the serum free control will be determined. The drug that causes the most proliferation will be chosen to test its’ ability to increase proliferation of cardiomyocytes in the sheep fetus in vivo.

A/Prof Janna Morrison 

The role of miR in regulating cardiac development

  

Does IUGR change the cardiac stem cell population?

 

Small babies, endothelial progenitor cells and increased risk of hypertension in adult life

Babies who are born small have an increased risk of cardiovascular disease in adult life. These include an increased risk of hypertension and left ventricular hypertrophy. We speculate that the small baby has a smaller pool of endothelial progenitor cells in fetal life due to a decrease in the supply of oxygen and nutrients to the fetus. A decrease in the pool of endothelial progenitor cells reduces the capacity for the development of endothelial cells and this may result in altered vessel formation. This altered vessel formation may lead to an increased risk of cardiovascular disease in adult life. We will use a model of placental insufficiency in sheep to study the gene expression of specific markers of endothelial progenitor cells in the heart, bone marrow and blood vessels in the fetus during late gestation.

A/Prof Janna Morrison and Dr Claudine Bonder

The role of bone in linking intrauterine growth restriction to proteins involved in metabolic syndrome in adult life

Being born small due to intrauterine growth restriction is associated with an increased risk of developing metabolic disorders in adult life. Previous studies have shown that the development of the liver before birth is significantly affected when fetal nutrient supply is low. Specifically, we have demonstrated that the expression of genes associated with glucose production and metabolism are altered. If these changes persist in postnatal life, it may explain the underlying cause of the hyperglycaemia seen in the development of metabolic disorders in adult life.

The role of the bone in determining metabolic risk is a developing area. This will be the first project to study the effects of fetal growth restriction on bone development and the metabolic factor, osteocalcin.

A/Prof Janna Morrison, Prof Caroline McMillen, Prof Howard Morris, Dr Paul Anderson

Pharmaceutical interventions in the battle against obesity

Currently more than half of all adults in Australia, the US and the UK are either overweight or obese and there are increasing rates of overweight and obesity in all age groups, including women of reproductive age. It is well established that individuals who grow slowly before birth and rapidly in early childhood have an increased risk of cardiovascular disease (CVD) and metabolic syndrome in adult life. What is not yet clear, however, is whether there is also an independent association between growing rapidly before birth and an increased risk of developing CVD. It has been variously reported in studies carried out in historical cohorts that there is: an increased risk of CVD at higher birth weights, a U shaped relationship between birth weight and CVD risk after adjustment for adult BMI or that there is an association between childhood BMI and CVD/metabolic syndrome risk which is independent of birth weight. The signal from the overnourished mother to the developing embryo may be related to insulin resistance. In this project, we will determine whether the insulin sensitiser, rosiglitazone, prevents the transmission of this signal and thus prevents the increased risk of metabolic syndrome in offspring. In this project we will study the impact of maternal overnutrition in late gestation on liver and muscle development in the sheep fetus.

A/Prof Janna Morrison, Prof Caroline McMillen, Dr Song Zhang

Linking intrauterine growth restriction to proteins involved in metabolic syndrome in adult life

Being born small due to intrauterine growth restriction is associated with an increased risk of developing metabolic disorders in adult life. Previous studies have shown that the development of the liver before birth is significantly affected when fetal nutrient supply is low. Specifically, we have demonstrated that the expression of genes associated with glucose production and metabolism are altered. If these changes persist in postnatal life, it may explain the underlying cause of the hyperglycaemia seen in the development of metabolic disorders in adult life.

A/Prof Janna Morrison, Prof Caroline McMillen

Does the preterm male fetus have greater cardiovascular vulnerability due to delayed cardiomyocyte maturation?

In Australia, 7% of babies are born preterm. Males are more vulnerable during the transition to living outside the womb. They experience more cardiovascular instability. We hypothesise that there is a delay in the maturation of the heart muscle cells in male fetuses that put the preterm male fetus at increased risk of cardiovascular collapse. We have shown that there is a delay in the terminal differentiation of cardiomyocytes in male fetuses. This is important because terminally differentiated cardiomyocytes can only get bigger. They can’t make more cardiomyocytes. But the undifferentiated cardiomyocytes, that can make more cardiomyocytes, can’t create as much force with each contraction of the heart. The growth of cardiomyocytes is regulated by a range of growth factors including the insulin-like growth factors (IGFs).

A/Prof Janna Morrison

Maternal Obesity and the Pathway to Childhood Obesity

Currently more than half of all adults in Australia, including women of reproductive age are either overweight or obese. Women who enter pregnancy with a high Body Mass Index have an increased risk of delivering a large baby with a high body fat mass and these babies in turn, have an increased risk of becoming obese in early childhood and later adult life. Thus heavier mothers have heavier babies and these babies are at risk of developing childhood obesity and becoming obese adults. It is not clear, however, how maternal obesity causes later obesity in the offspring and initiates this intergenerational cycle of obesity. Maternal obesity may result in childhood obesity as a result of exposure of the early embryo, the developing placenta and/or the fetus to maternal over-nutrition. It is important to understand the effects of maternal over-nutrition on the embryo, placenta and fetus as this will influence recommendations on the timing and nature of nutritional interventions in pregnancy designed to limit the impact of maternal obesity on the intergenerational cycle of obesity.

A/Prof Janna Morrison, Prof Caroline McMillen

What is the role of the IGF signalling system in heart development?

In Australia, intrauterine growth restriction occurs in 7% of babies. Large studies show that these babies are at an increased risk of suffering from heart disease in adult life. The mechanisms that link these events are not clear. We have, however, shown that the IGF-1 receptor signalling pathway plays an important role in heart growth in late gestation and this pathway is altered in growth restricted fetuses. We hypothesise that up regulation of components of the IGF-1 receptor signaling pathway result in changes in heart development in growth restricted fetuses.

A/Prof Janna Morrison and Prof Doug Brooks

Effects of Periconceptional nutrition (in vivo and ex vivo) on fetoplacental and postnatal development

A number of studies in the human and animal models have demonstrated that the period around the time of conception (oocyte and early embryo development and during early gestation), the periconceptional environment, can have a substantive impact on fetoplacental development. In particular, maternal under-nutrition/over-nutrition during the periconceptional period or exposure of an embryo to in vitro culture (involved in in vitro fertilisation and assisted reproductive technologies) can lead to an alteration in cardiovascular, renal and placental function. In addition, changes to the periconceptional environment during early embryo development may “program” the timing of birth. We are currently investigating how the environment of the developing embryo during the first seven days of life causes changes in prenatal and postnatal growth, cardiovascular and renal function and the development of adult diseases such as cardiovascular disease and obesity. This project will use real-time PCR to analyse gene expression in tissue collected from fetuses and lambs that were exposed to a periconceptional insult, either maternal undernutrition in the 3 wks around conception or in vitro culture. The student will gain skills in animal handling and care as well as real-time PCR analysis of gene expression.

Dr Song Zhang, Prof Caroline McMillen and A/Prof Janna Morrison

Blood pressure regulation and heart rate variability: role of fetal growth and hypoxia

Growth restricted fetuses have the same blood pressure as normally grown fetuses but are at increased risk of hypertension in adult life. This predisposition to hypertension is established in prenatal life when blood pressure regulation is more reliant on the sympathetic and rennin angiotensin systems. The role of hypoxia versus absolute growth restriction is not fully understood. This project will compare blood pressure, blood pressure regulation, heart rate and variability in heart rate in fetuses that are normoxic or hypoxic, normally grown or growth restricted.

A/Prof Janna Morrison and Prof Caroline McMillen

Role of nutrition on surfactant development in the fetus

This project is a collaboration between two research groups in the Sansom Institute for Health Research - the laboratory for ‘Molecular & Evolutionary Physiology of the Lung’ and the’ Early Origins of Adult Health Research Group’. In the placental restriction model, the growth restricted fetus experiences both nutrient and oxygen restriction (i.e. under-nutrition & hypoxia). We hypothesise that hypoxia has the dominant effect on surfactant maturation. To determine the contribution of under-nutrition alone, we wish to examine surfactant maturation in mid- to late gestation sheep fetuses exposed to maternal under-nutrition. In this project lung tissue and plasma from control and undernourished sheep fetuses will be analysed for alterations in surfactant protein and gene expression and plasma glucose and cortisol concentrations. Futhermore, babies born preterm or born small for their gestational age are at an increased risk of developing respiratory distress. We wish to establish the mechanisms and timing of surfactant maturation during late gestation in relation to environmental factors that lead to intrauterine growth restriction.

A/Prof Sandra Orgeig and A/Prof Janna Morrison

Areas of study and research

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