Understanding The Regulation Of HERG Potassium Channel In The Myometrium At The Time Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$597,661.00
Summary
We have shown that a potassium channel known as hERG falls precipitously at the time of term labour and that blocking this channel causes powerful uterine contractions. This grant will determine how the expression of this channel is regulated in the myometrium and whether changes in hERG channels also occur in premature labour.
Preclinical Development Of TLR Signalling Inhibitors For Prevention Of Preterm Labour And Fetal Inflammatory Injury
Funder
National Health and Medical Research Council
Funding Amount
$690,821.00
Summary
Preterm birth affects 8% of Australian births and is a major cause of infant and child health problems. Therapies to prevent or delay prematurity are urgently required. This study will investigate new drugs that suppress the triggers of preterm labour. We will evaluate drug effects in mice and human placental tissue, to demonstrate safety and fetal protection from inflammatory injury that occurs with prematurity. Successful completion of the study is expected to lead to clinical trials in women.
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