Roles Of PTHrP And Calcium In Mammary Function In Perinatal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Babies that are born small have significant problems around the time of birth and may have limited catch-up growth. A recently discovered protein known as PTHrP influences the nutrition of the growing newborn through breast milk. Because of its potential importance to small babies we intend to study this protein during and after pregnancy in rats and their pups. New treatments may emerge from the knowledge gained from these studies that may improve the growth and health of infants.
Antenatal Insulin-like Growth Factor-I And Perinatal Growth, Survival And Function Of The Growth Restricted Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$150,370.00
Summary
Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUG ....Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.Read moreRead less
Insulin-like Growth Factor (IGF) -II, Cytotrophoblast Migration And Placental Development
Funder
National Health and Medical Research Council
Funding Amount
$487,750.00
Summary
During pregnancy, placental cells invade into the uterus and tap into the maternal blood vessels to procure an adequate blood supply for the growth of the placenta and hence the fetus. If this invasion process is impaired early in pregnancy, then the woman may suffer a miscarriage, if the process is impaired in mid-pregnancy then the mother may develop preeclampsia in which her blood pressure goes up and, in severe cases, placing her life and that of her unborn baby at risk. Miscarriage occurs i ....During pregnancy, placental cells invade into the uterus and tap into the maternal blood vessels to procure an adequate blood supply for the growth of the placenta and hence the fetus. If this invasion process is impaired early in pregnancy, then the woman may suffer a miscarriage, if the process is impaired in mid-pregnancy then the mother may develop preeclampsia in which her blood pressure goes up and, in severe cases, placing her life and that of her unborn baby at risk. Miscarriage occurs in 10-15% of pregnancies and preecclampsia in 7% of pregnancies. Preecclampsia may be life-threatening in up to 3% of all pregnancies and is a major cause of maternal death in pregnant women in Western countries. This project will examine the effect of treatment of the pregnant guinea pig with insulin-like growth factor-II on placental cell invasion and the capacity of the placenta to deliver nutrients to the fetus. We will also determine whether the effects of this treatment are mediated by a specific membrane receptor on the cell surface of the invading placental cells. We predict that this growth factor will enhance placental cell invasion and improve placental function. If this is the case then our findings may be developed for use in women at risk, to improve placental function and hence maternal and fetal health.Read moreRead less
Fetal Cardiovascular Development And The Impact Of Chronic Hypoxia And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$307,232.00
Summary
Low birth weight occurs in 7% of Australian babies and is associated with an increased risk of cardiovascular disease in adult life. Understanding the mechanisms underlying heart and blood vessel development in low birth weight babies will lead to improved identification and intervention in those individuals at risk of cardiovascular disease in adult life, improving heart health for Australians. Reducing cardiovascular disease will improve both quality and quantity of life for Australians.
Diagnostic Tests To Predict Risk For Life Threatening Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$682,824.00
Summary
The main complications of pregnancy, preeclampsia, preterm birth and intrauterine growth restriction afflict 19% of first pregnancies and are life threatening to the mother or baby in 6% of pregnancies. Currently we have no way of knowing which women will suffer these diseases until symptoms manifest. We aim to develop genetic tests that can predict which women are at risk. This will permit earlier interventions that will improve the health of pregnant women and their babies.
Physical Determinants Of Lung Development Before And After Birth
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or i ....Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or it may be due to inappropriate lung development during fetal life. It is important therefore, to understand the mechanisms that control growth and development of the lung both before and after birth. During fetal life the lungs are filled with liquid which expands the lungs and provides a stretch stimulus causing them to grow. Previously we have shown that a reduction in the degree of fetal lung expansion causes lung growth to cease. Likewise, if we increase the degree of lung expansion in the fetus, we induce a rapid increase in fetal lung growth and maturation. This stimulus is so potent that it can reverse an existing lung growth deficit, thus enabling survival of the newborn. In this application we will investigate the mechanisms by which alterations in lung expansion induce growth and maturation of the lung. Specifically we will investigate the role of calmodulin in fetal lung growth, because the genes that encode it are activated when the lung cells are growing most rapidly. In addition, we will identify other genes that are turned on or off during rapid growth of the lung because those genes are likely to play important roles in the regulation of fetal lung growth and development. We will also investigate the underlying differences in the control of lung growth at different stages of gestation, as well as investigate factors that regulate lung growth after birth, particularly in prematurely born animals.Read moreRead less
Optimising The Bone And Cardiovascular Response To Dietary Calcium: A Physiological Approach In Experimental Models
Funder
National Health and Medical Research Council
Funding Amount
$35,670.00
Summary
We aim to identify a variable calcium diet that optimises bone mass, density and strength as well as blood pressure in a rat model of intrauterine growth restriction. We propose that a moderate calcium diet followed by a high calcium diet is beneficial for bone and heart health. This is based on the physiological effect of reduced calcium intake stimulating intestinal calcium absorption. This represents a novel research approach to improving calcium intake, bone as well as heart health.
Leptin And Development: A Role In The Transition At Birth
Funder
National Health and Medical Research Council
Funding Amount
$100,380.00
Summary
A series of epidemiological studies have demonstrated that life expectancy and the risk of developing a range of adult diseases such as heart disease, diabetes mellitus and obesity, are related to weight and size at birth. It appears that genetic and environmental factors interact during pregnancy to determine the growth rate of the embryo and fetus and result in a permanent programming of the development of fetal organs and tissues which may result in the onset of disease in adult life. It is w ....A series of epidemiological studies have demonstrated that life expectancy and the risk of developing a range of adult diseases such as heart disease, diabetes mellitus and obesity, are related to weight and size at birth. It appears that genetic and environmental factors interact during pregnancy to determine the growth rate of the embryo and fetus and result in a permanent programming of the development of fetal organs and tissues which may result in the onset of disease in adult life. It is well established that babies born to mothers who develop diabetes in pregnancy are bigger at birth and are at greater risk of developing obesity in childhood. Paradoxically several major studies of human populations exposed to deprivation during pregnancy have shown that children born to mothers who experience undernutrition in pregnancy may also develop obesity in adult life. A new hormone has recently been identified which acts as a signal of fat mass and which plays a major role in the regulation of body weight and energy expenditure in the adult. We propose to define the role of this hormone before birth and to determine whether its production or action is altered by an increase or a decrease in fetal nutrition. In particular, we will investigate whether perturbations in the metabolic environment of the fetus program an increased production of this hormone or resistance to its actions after birth. These studies will increase our understanding of what adaptive changes before birth may relate to an increased likelihood of obesity after birth.Read moreRead less