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Epigenetic Regulation Of Inflammatory Genes In The Fetal Membranes: Role In Term And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$468,534.00
Summary
Preterm birth is the leading cause of death among newborns and the biggest contributor to disability among infants. Here we propose research to define the mechanism that controls the length of pregnancy and is disrupted in preterm birth. Specifically, we will determine what causes the repression of the labour-promoting inflammatory genes in the uterus during pregnancy and what activates them at labour. We will identify new targets for interventions to block or prevent preterm birth.
Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not ....Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not very effective. We have recently identified a novel pathway that regulates the activity of the muscle cells that form the uterus. This project seeks to understand the biochemical processes that change a muscle cell so that it begins to contract actively at the end of pregnancy. Specifically the project will examine two proteins called HSP20 and HSP27. These proteins have recently been reported to play a critical role in the contraction and relaxation of smooth muscle cells in the heart and blood vessels. We have identified for the first time that these proteins are also present in the muscle of the human uterus. It is likely that they play a critical role in regulating the contractions of the uterus. By understanding this process better we may be able to design better treatments to prevent premature birth.Read moreRead less
Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not ....Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not very effective. Our work has shown that a hormone called corticotrophin releasing hormone (CRH) made in the placenta plays a critical role in determining the length of a pregnancy. We have measured the levels of this hormone in the blood of pregnant women and shown that it increases more rapidly than normal in women who deliver prematurely and more slowly than normal in women who deliver late. It acts as a kind of clock to determine the length of pregnancy. What is not known is how this hormone acts to bring on labour. What is particularly puzzling is that some of the actions of the CRH seem likely to cause the uterus to relax rather than to contract. We wish to test the idea that the rapidly rising levels of this hormone in late pregnancy cause changes in the uterus that stop the pathways to relaxation and lead to contraction. To perform these studies we will use small pieces of uterus donated with informed consent from women undergoing caesarean section. The results of these studies may allow us to design better ways of preventing premature birth and prevent many cases of cerebral palsy and intellectual handicap.Read moreRead less
This project will test if the ratio of the two different estrogens found in the blood of pregnant women is the critical factor in determining the onset of contractions in the uterus at labour. The studies will also determine the role of a newly discovered receptor for estrogens in allowing powerful contractions at labour. Results will allow development of new treatments to prevent premature birth that block the actions of estrogen at this new receptor or change the ratio of the two estrogens.
Inflammatory Pathways For Novel Therapeutic Interventions In Preterm Delivery
Funder
National Health and Medical Research Council
Funding Amount
$568,006.00
Summary
Preterm birth is common and carries severe risks for the child. Existing therapies are not very successful in arresting preterm labour or improving outcomes for the fetus. We have discovered that blocking inflammatory ‘sensor’ molecules can slow labour progression. This project will (1) increase our knowledge of the inflammatory pathways that initiate early labour, and (2) define the mechanism of action and safety of a new drug that has potential for delaying preterm birth in women.
The Intrarenal Renin Angiotensin System (RAS) In Indigenous Women: An Early Indicator Of Renal Dysfunction In Women At Risk Of Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$645,358.00
Summary
Indigenous women are twice as likely to have low birth weight babies compared to non-Indigenous women and 2.5 times as likely to develop preeclampsia, possibly because they have a much greater incidence of chronic kidney disease, predisposing them to these pregnancy outcomes. We have found a new, sensitive marker of early stage renal dysfunction in pregnancy that could be useful for detecting early stage renal disease and which is indicative of an increased risk of adverse pregnancy outcome.