The Mechanisms That Regulate The Onset Of Human Labour And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$528,170.00
Summary
Reproductive biologists still cannot explain the molecular mechanisms that govern human birth. This lack of knowledge prevents the development of better moitoring and treament of complications of labour and delivery. If we are to provide the best possible start to life and improve newborn health care delivery then we must: (1) better understand what triggers labour; (2) determine whether there are biomarkers that we can use to identify women at risk of early birth; and (3) identify new ways to d ....Reproductive biologists still cannot explain the molecular mechanisms that govern human birth. This lack of knowledge prevents the development of better moitoring and treament of complications of labour and delivery. If we are to provide the best possible start to life and improve newborn health care delivery then we must: (1) better understand what triggers labour; (2) determine whether there are biomarkers that we can use to identify women at risk of early birth; and (3) identify new ways to delay birth. This is the overall objective of this research project. In particular, this project focuses on how the multiple events needed to achieve a successful outcome to pregnancy are coordinated at the time of birth.Read moreRead less
Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.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
The Role Of The Intrauterine (pro) Renin-(pro)renin Receptor System In Prostaglandin Synthesis In Pregnancy.
Funder
National Health and Medical Research Council
Funding Amount
$488,478.00
Summary
Preterm birth is associated with a very high incidence of infant disability and mortality. This has long term economic and social costs to the Australian people. We will demonstrate that in late gestation, the intrauterine (pro)renin renin receptor system controls prostaglandin synthesis by the fetal membranes and the placenta. Prostaglandins can cause premature labour.
Developing Molecularly Targeted Therapeutics And Diagnostics For Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$321,489.00
Summary
Pregnancy complications still causes the death of mothers, and their babies. During this fellowship, we will be developing new treatments and clinical tests for three important complications of pregnancy. We will run clinical trials of a new medication based treatment to cure ectopic pregnancies. We will also develop a blood test that can identify those babies still in the womb but suffering dangerously low oxygen levels. Lastly, we will develop drugs to treat preeclampsia, a serious condition o ....Pregnancy complications still causes the death of mothers, and their babies. During this fellowship, we will be developing new treatments and clinical tests for three important complications of pregnancy. We will run clinical trials of a new medication based treatment to cure ectopic pregnancies. We will also develop a blood test that can identify those babies still in the womb but suffering dangerously low oxygen levels. Lastly, we will develop drugs to treat preeclampsia, a serious condition of pregnancy.Read moreRead less