Investigation Of A New Hypothesis That Increased TGF? Activity In Developing Fetal Organs Predisposes A Women To Polycystic Ovary Syndrome And Associated Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
Have you ever wondered why some people get fat and other do not, no matter how much they eat? The answer could lie in what happened before they were born. This project investigates a new hypothesis that was developed from discoveries on polycystic ovary syndrome. Women with this syndrome are at increased risk of becoming overweight and diabetic. If the hypotheses prove correct it might be possible to reduce the incidence of these metabolic disorders in the longer term.
Perinatal And Intergenerational Influences On Adult Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
The aim of this project is to determine the effects of restriction of nutrient supply before and after birth on growth and the development of adult onset diabetes. Being born small and its associated neonatal catch-up growth independently predict adult diabetes. Placental restriction is a major cause of reduced nutrition and growth before birth and is implicated in this programming of disease. Our novel findings suggest that placental compromise increases appetite but also impairs milk quality a ....The aim of this project is to determine the effects of restriction of nutrient supply before and after birth on growth and the development of adult onset diabetes. Being born small and its associated neonatal catch-up growth independently predict adult diabetes. Placental restriction is a major cause of reduced nutrition and growth before birth and is implicated in this programming of disease. Our novel findings suggest that placental compromise increases appetite but also impairs milk quality and supply which limits overfeeding and catch-up growth initially, but on weaning, may independently lead to diabetes. We will determine if this is a direct result of poor nutrition and made worse by overfeeding in response to restored nutrition. We hypothesize that placental compromise permanently reduces an individual's metabolic capacity and that the extent of availability of nutrition after birth determines the consequences for insulin action and increased body fat. Manipulations of postnatal nutrition (by cross-fostering) and fat oxidation will be performed, which are pivotal to understanding the roles of catch-up growth and increased food intake in disease onset. We have found that cross-fostering small rat pups at birth onto mothers with normal lactation improves growth during lactation. The proposed studies will establish the cross-fostering effect on the development of diabetes and identify a developmental stage during which nutritional or other manipulations may have beneficial consequences for the health of the breastfeeding small infant. We propose to determine whether adult females, exposed to placental restriction as a fetus, produce offspring that develop diabetes, and establish whether this effect is caused by programming before conception and-or an altered fetal environment. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health.Read moreRead less
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Novel Therapy For Enhancing Organ Maturation In Pre-term Babies
Funder
National Health and Medical Research Council
Funding Amount
$694,323.00
Summary
This project is developing a factor to enhance organ maturation and repair that may provide a new therapy for premature babies and fetuses with birth defects. This exciting new finding allows for the development of treatments of underdeveloped organs, in particular the lungs of premature and growth restricted babies. We are also trialing this factor in unborn babies with defects to the kidneys and lungs of which there is currently no cure.
Creatine Supplementation In Pregnancy: Utilising Cells’ “Built-In” Energy Buffering System
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Through pregnancy, the placenta transfers oxygen and nutrients from the mother to the baby. When a placenta doesn’t function properly a baby’s health is compromised. This can lead to morbidity or death. Creatine is the “back-up generator” of all cells and could help the failing placenta increase nutrient and oxygen delivery to the baby. This study will develop creatine as a potential new therapeutic, to improve the survival of babies of complicated pregnancies.
The Effects Of Maternal Glucocorticoid Administration In Growth Restricted Fetuses.
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are th ....Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are therefore likely to receive maternal betamethasone. From both human observations and animal studies, it is well documented that IUGR fetuses demonstrate a range of cardiovascular adaptations that ensure maintenance of oxygen delivery to vital organs despite reduced placental perfusion. However, in recent clinical and experimental studies we have demonstrated that administration of betamethasone to IUGR fetuses induces changes in fetal blood flow that may be detrimental to the IUGR fetus. Specifically, we believe that glucocorticoids may increase the risk of both cardivascular and cerebral damage in the growth restricted fetus. The significance of these findings and the mechanisms regulating these changes remain unclear but they have clear implications for future clinical management. This proposal represents the further development of preliminary experimental studies to examine the effects of betamethasone in the ovine IUGR fetus with future clinical care in mind.Read moreRead less
The Role Of Proteoglycans In Contributing To Placental Thrombosis And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$368,269.00
Summary
Fetal growth restriction (FGR) is a pregnancy complication in which the baby doesn�t grow properly in the womb. Growth restricted babies are much more likely to be stillborn. These babies are also at risk of problems later in life such as obesity, diabetes and heart disease. This study investigates molecules in the placenta that may be responsible for causing FGR. If we can understand how these molecules cause the problem of FGR, we may be able to find better ways of treating or preventing it.
Prenatal Placental And Postnatal Mammary Programming Of Cardiovascular And Renal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$503,776.00
Summary
Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat mo ....Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat model, we will determine for the first time if restricted nutrition before birth via the placenta or after birth via lactation increases the risk of developing high blood pressue and kidney and blood vessel dysfunction. Manipulations of nutrition after birth will be achieved by cross-fostering studies. We will establish whether a reduction in the number of functioning units (nephrons) in the kidney, alterations in key genes involved in kidney development and changes in blood vessel reactivity are associated with developing hypertension. We will manipulate the renin-angiotensin system (RAS), which is important in determining kidney function, to define its role in hypertension in this model. We propose that a common lifestyle insult, such as modest elevation in dietary salt, will evoke exaggerated responses in adult offspring who were born small. These studies will identify the mechanisms by which the kidney, vasculature and RAS contribute to the programming of hypertension and the relative roles of the prenatal and postnatal environments. Defining the underlying mechanisms responsible will provide insight into early life interventions that may lessen these adverse consequences for longer-term health. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health in this emerging field.Read moreRead less
My research is primarily aimed at understanding the physiology and pathophysiology of lung development; in particular, how lung development is affected by the fetal and neonatal environment such that adult lung function and respiratory health are impaired. In addition to the lung my research examines the effects of the prenatal environment on development of the brain and cardiovascular system.
Can Exercise And Improved Nutrition Normalise Rat Skeletal Muscle Mitochondrial Biogenesis Following Growth Restriction?
Funder
National Health and Medical Research Council
Funding Amount
$338,128.00
Summary
Being born small is associated with the development of adult diseases such as insulin resistance, cardiovascular disease and type 2 diabetes. Mitochondria are responsible for generating energy within all cells and impaired mitochondrial function is implicated in the development of these diseases. We have exciting preliminary data demonstrating that being born small impairs the synthesis of mitochondria in adult rat skeletal muscles. This project will determine if lifestyle interventions such as ....Being born small is associated with the development of adult diseases such as insulin resistance, cardiovascular disease and type 2 diabetes. Mitochondria are responsible for generating energy within all cells and impaired mitochondrial function is implicated in the development of these diseases. We have exciting preliminary data demonstrating that being born small impairs the synthesis of mitochondria in adult rat skeletal muscles. This project will determine if lifestyle interventions such as exercise and improved nutrition after birth in rats that were born small can normalise the molecular signals responsible for mitochondrial synthesis in muscle. Understanding these mechanisms responsible for mitochondrial function will provide insight into early life interventions that may lessen the adverse consequences of being born small. This research will increase the likelihood that practical public health interventions can be developed to improve adult health.Read moreRead less