Molecular Mechanisms Regulating Spontaneous Onset Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
The single most important complication contributing to poor pregnancy and neonatal outcome is premature birth. If we are to provide the best possible start to life, improve perinatal health and reduce the risk of developing adult disease . A better understanding of labour is requisite to improving health care delivery during pregnancy and outcomes for both mother and baby. This reserach project will investigate the how labour-associated events are reguluated by nuclear proteins.
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.
Adults who were small at birth have a higher risk of coronary heart disease and adult onset diabetes. From a public health point of view the most important issue is to identify which factors in pregnancy cause low birthweight and lead to increased risk of adult disease. Growth of a fetus depends on the supply of oxygen and nutrients and the availability of nutrients will depend on both the mother's dietary intake and the transfer of nutrients, via the placenta, to the baby It is important that w ....Adults who were small at birth have a higher risk of coronary heart disease and adult onset diabetes. From a public health point of view the most important issue is to identify which factors in pregnancy cause low birthweight and lead to increased risk of adult disease. Growth of a fetus depends on the supply of oxygen and nutrients and the availability of nutrients will depend on both the mother's dietary intake and the transfer of nutrients, via the placenta, to the baby It is important that we understand the role of maternal nutrition in fetal growth because it is potentially modifiable. Although we know that birthweight falls in times of famine little is known about whether the composition of a mother's diet in a developed society affects birthweight and later health of the offspring. We plan to study this in twin pregnancies, since maternal nutrition is more stretched and any effects should be magnified and more readily identified. It may be that maternal nutrition only matters if the placenta is not working as well as it should. Unfortunately there is no good measure of how well the placenta is working, but we will measure erythropoietin level in infants as a marker of whether they were getting enough oxygen via the placenta, and see whether there is any evidence that maternal nutrition matters more as the infant shows more signs of poor oxygen supply. In twins we can look between pairs for evidence that maternal nutritional factors affect birthweight, at twins within pairs to see whether oxygen supply or other individual factors are important and we can compare all infants as individuals to see how these different factors interact. We plan to study 200 women with twin pregnancies in Melbourne and Adelaide. Once we have identified factors influencing birthweight, we will be in a position to plan future studies to determine which are associated with increased risk markers for cardiovascular diseaseRead moreRead less
The Impact Of Severe Asthma During Pregnancy On Placental Function And Fetal Hypothalamic-pituitary-adrenal Function
Funder
National Health and Medical Research Council
Funding Amount
$209,242.00
Summary
This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased ....This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased intake of glucocorticoids for the treatment of asthma during pregnancy changes how the placenta functions and allows the fetus to be exposed to maternal glucocorticoids causing changes in fetal development. We will examine placental blood flow and measure some placental enzymes that may be involved in the control of blood flow in placentas collected from women with mild, moderate and severe asthma and compare them to non-asthmatic women. We will look at placental blood flow in utero using Doppler ultrasound and also in vitro after the placenta is delivered. We want to see if the fetus is affected by increased intake of glucocorticoids by the mother by measuring a hormone estriol, which originates from the fetus. We will measure estriol throughout pregnancy as it can easily be detected in the mothers' urine. These studies will tell us if glucocorticoid intake for the treatment of asthma can exert effects on the placenta and baby during pregnancy. These studies will make a significant contribution both scientifically and clinically. At a scientific level we will be able to examine how increased maternal glucocorticoid intake during pregnancy affects placental mechanisms and whether these changes affect the fetus and clinically the outcome of this study will allow us to optimize asthma therapy during pregnancy so that we can improve the outcome for the baby.Read moreRead less
Differential Effects On Fetal Growth And Development Of Repeated Fetal Or Maternal Corticosteroid Treatments
Funder
National Health and Medical Research Council
Funding Amount
$356,849.00
Summary
Injections of synthetic hormones (corticosteroids) to women at risk of early preterm birth reduce the rate of respiratory illness and death in the newborn infant. It is standard clinical practice prior to early preterm birth to give corticosteroids by intramuscular injection to the mother. For many women, however, preterm birth does not occur as expected and it has become common practice to give repeated courses of corticosteroids to women in whom the risk of preterm delivery recurs or continues ....Injections of synthetic hormones (corticosteroids) to women at risk of early preterm birth reduce the rate of respiratory illness and death in the newborn infant. It is standard clinical practice prior to early preterm birth to give corticosteroids by intramuscular injection to the mother. For many women, however, preterm birth does not occur as expected and it has become common practice to give repeated courses of corticosteroids to women in whom the risk of preterm delivery recurs or continues. Using the sheep model, we have shown that repeated doses of corticosteroids, given intramuscularly to the mother, are of benefit to newborn lung function, but also reduce the rate of fetal growth and adversely affect brain development. Evidence from the Western Australian Preterm Infant Cohort Study suggests that birthweight in humans is similarly affected by repeated corticosteroids and is followed by behavioral disorders in childhood. Using sheep, we have shown that repeated injections of corticosteroids given directly to the fetus cause no reduction in birthweight although maturation is still enhanced. This finding of a differential effect of corticosteroids by different routes of administration raises several exciting opportunities and questions. First is the possibility that direct fetal treatment may be of use in humans, if current human trials show that repeated doses cause effects similar to those we have seen in sheep. Secondly, the finding challenges our current understanding of how an individual may be programmed for subsequent health or illness by prenatal events. The proposed study will attempt to explain why corticosteroids given to the mother, but not the fetus, restrict fetal growth. Our hypothesis is that these hormones, when given repeatedly to the mother, adversely affect the ability of the placenta to transfer essential nutrients to the fetus. We will test this hypothesis using pregnant sheep in which catheters have been implanted surgically.Read moreRead less
Role Of Endogenous Opioid Peptides In Endometrial Receptivity And Placentation
Funder
National Health and Medical Research Council
Funding Amount
$523,884.00
Summary
Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth w ....Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth weight are much more likely to develop a host of diseases including cardiovascular disease, diabetes and obestiy in adult life increasing the long term burden of health care support. Infertility is often due to the lack of uterine endometrial receptivity while the pregnancy complications arise from the reduced growth of the placenta and sub-optimal interactions between the mother's uterus and the growing placenta. Endometrial infertility, placental growth and interactions with the endometrium is stringently regulated by substances produced at the maternal endometrial- placental interface. To understand how infertility and pregnancy complications arise, develop diagnostic, monitoring and therapeutic tests it is critical to understand the roles played by these regulatory substances. We have novel data suggesting that small proteins known as endogenous opioids could be enchancing endometrial receptivity and the growth and development of the placenta. Interstingly these substances are closely related to exogenous opioids such as heroin and morphine. We will investigate the manner in which these substances regulate endometrial immune cell function, maintain the endometrial stromal cell bed in preparation for pregnancy and direct the growth and differentiation of the placenta. The findings will give novel insights into infertility, improve the success rates of in vitro fertilization, reduce maternal and neonatal complications of pregnancy.Read moreRead less
Glucocorticoid-progesterone Interactions In The Control Of Fetal And Placental Growth
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The growth and function of the placenta is of critical importance to the successful maintenance and completion of human pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes, and coordination of homone signals that regulate fetal growth and development. If the placenta does not perform these functions adequately, the growth rate of the fetus is compromised and can lead to difficulties before and after birth. This project exami ....The growth and function of the placenta is of critical importance to the successful maintenance and completion of human pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes, and coordination of homone signals that regulate fetal growth and development. If the placenta does not perform these functions adequately, the growth rate of the fetus is compromised and can lead to difficulties before and after birth. This project examines how two important steroid hormones, progesterone and glucocorticoids, interact with growth factors in the placenta to control its growth and function. Progesterone is recognized as 'the hormone of pregnancy' as it helps the mother adapt to pregnancy. Progesterone may also affect the placenta by regulating its synthesis and breakdown of other hormones, and the balance between placental cell proliferation and death. These effects of progesterone will be studied in this project. We will also examine how glucocorticoid hormones regulate the growth and function of the placenta. Glucocorticoids are structurally very similar to progesterone, and are secreted by the adrenal gland in increased quantities during pregnancy. Glucocorticoids exert a wide range of effects on the mother, placenta and fetus; indeed, glucocorticoids are recognized clinically as the single-most importnat signal for fetal maturation in late pregnancy. However, too much glucocorticoid retards fetal and placental growth, and in this project we will study how this occurs in the placenta, and how the placenta may protect itself from detrimental effects of glucocorticoids. We will test whether placental growth is restricted by glucocorticoids through their effects on placental growth factor hormones. Overall, these studies could have important implications for the clinical management of pregnancy, particularly in relation to fetal and placental growth.Read moreRead less
Novel Actions Of Leptin In Implantation And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of f ....The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of fetal growth. In human pregnancy, the placenta becomes an additional major source of leptin, and this is secreted into the mother and the fetus. Recent work in animal models also indicates that the process of implantation, whereby the embryo embeds itself in the lining of the uterus and establishes a placenta, cannot proceed in the absence of leptin. But how leptin exerts these critical effects on the implantation process and placental function is not known. In this study we will explore several potential actions of leptin in the uterus and placenta, and examine whether the leptin signaling system is aberrant in cases where the fetus does not grow normally. Of particular interest is the possible interaction of leptin with another group of important signaling molecules called the peroxisome proliferator-activated receptors, or PPARs. One of these, PPAR-gamma, plays an indispensable role in the establishment of the placenta, particularly in relation to the formation of blood vessels, a process that is also a target for leptin action. Several lines of evidence, most notably in fat cells, suggest that both PPAR-gamma and leptin regulate common aspects of cell function. Such interactions provide us with important clues as to how leptin and the PPARs could work together to promote the optimal establishment, growth and function of the placenta, and these will be explored in this project.Read moreRead less