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
An In Vitro Study Of The Mechanisms Underlying Ineffective Labour In Women
Funder
National Health and Medical Research Council
Funding Amount
$326,820.00
Summary
Strong contractions of the uterus are necessary for successful vaginal delivery of the baby. Failure of the uterus to contract forcefully, ineffective labour, is a major cause of caesarean delivery. Drip infusion of oxytocin is routinely used in attempts to strengthen the weak contractions of ineffective labour, but this is not always successful in bringing about vaginal delivery. The normal preparation of the uterus for the process of birth is likely to involve a complex array of processes. The ....Strong contractions of the uterus are necessary for successful vaginal delivery of the baby. Failure of the uterus to contract forcefully, ineffective labour, is a major cause of caesarean delivery. Drip infusion of oxytocin is routinely used in attempts to strengthen the weak contractions of ineffective labour, but this is not always successful in bringing about vaginal delivery. The normal preparation of the uterus for the process of birth is likely to involve a complex array of processes. The failure to successfully resolve ineffective labour, other than by caesarean section, stems from a lack of understanding of these processes. In our studies of the human uterus over the past few years we found that the behaviour of samples obtained from women undergoing caesarean section during labour was quite variable. Some samples possessed a high degree of negative electricity which made contraction difficult. Some other samples were quite resistant to the contracting effects of oxytocin. In yet a third group, the uterus did not contract when given prostaglandin, one of the body's most important hormones during labour. When the obstetricians checked the medical records of these women, they found that ineffective labour had been diagnosed. The aim of this study is to work out the details of what is happening in these cases of ineffective labour. Since this problem is a major cause of caesarean delivery, a greater understanding of the underlying causes will facilitate the development of more effective treatments and hence bring about a resolution which is fundamental to healthy mothers and babies.Read moreRead less
Regulation Of Prostaglandin Endoperoxide Synthase-2 In The Human Fetal Membranes At Birth
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, an ....Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, and an increase of prostaglandin levels in the uterus is likely responsible for inducing labour both normally and preterm. We have previously identified an enzyme protein in the fetal membranes, called prostaglandin synthase-2, that has a key role in the synthesis of intrauterine prostaglandins during pregnancy. This enzyme is increasingly expressed before labour onset. In the present application, we propose studies to determine what causes the increased expression. We hypothesize that the gene encoding this enzyme is specifically activated in the fetal membranes in preparation for labour. We will define the mechanism of regulation by determining the activity of the gene in tissues from women who deliver either spontaneously or without labour at term and preterm. Further, we will determine the interaction of regulatory proteins with the prostaglandin synthase-2 gene in these pregnancies in order to understand the mechanisms of regulation at the molecular level. Finally, we will conduct cell culture studies to experimentally manipulate prostaglandin synthase-2 gene activity in fetal membrane cells. As an overall outcome of this work, new targets may be identified for drugs to disrupt prostaglandin synthase-2 gene activation specifically in the fetal membranes. The long term perspective is to block prostaglandin synthesis in the uterus in order to suppress preterm labour and prevent preterm birth.Read moreRead less
Characterisation Of Immune Regulators In The Human Myometrium.
Funder
National Health and Medical Research Council
Funding Amount
$85,285.00
Summary
Premature birth is a major cause of perinatal death and morbidity. It further predisposes the individual to increased morbidity throughout life. Although the mechanism of birth has been heavily researched with an objective of preventing preterm babies, it is still not fully understood. A major problem has been the lack of suitable and accessible animal models. A key organ coordinating the birth event is the uterine smooth muscle, myometrium. For effective birth and delivery, the myometrium needs ....Premature birth is a major cause of perinatal death and morbidity. It further predisposes the individual to increased morbidity throughout life. Although the mechanism of birth has been heavily researched with an objective of preventing preterm babies, it is still not fully understood. A major problem has been the lack of suitable and accessible animal models. A key organ coordinating the birth event is the uterine smooth muscle, myometrium. For effective birth and delivery, the myometrium needs to be contracting synchronously in a coordinated manner to dilate the cervix while pushing the fetus into position for eventual delivery through the birth canal. This project aims to characterise the molecular events occurring at the myometrium which precedes and precipitates labour. These local changes will be linked with the systemic hormonal changes in order to approach a model for human parturition.Read moreRead less
A Double Blind Randomised Placebo Controlled Trial Of Melatonin As An Adjuvant Agent In Induction Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$384,566.00
Summary
Induction of labour, a common obstetric intervention fails in almost 40% of first time mothers. There is evidence to suggest that the endogenous hormone melatonin has important roles in the progress of labour. We will undertake a double-blind randomised placebo controlled trial of melatonin supplementation to improve the success of induction of labour in first time mothers. We will also assess the economic impact of melatonin supplementation at induction of labour.
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.
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Managing an ageing population for income adequacy and fiscal sustainability. This project aims to improve understanding of the impacts of existing key reforms intended to ease fiscal pressures associated with population ageing. The right mix of retirement income policies is vital to Australia's fiscal sustainability, however the effectiveness of existing policies is unknown. The project expects to identify impacts of key reforms on employment, re-training, income, savings and future retirement i ....Managing an ageing population for income adequacy and fiscal sustainability. This project aims to improve understanding of the impacts of existing key reforms intended to ease fiscal pressures associated with population ageing. The right mix of retirement income policies is vital to Australia's fiscal sustainability, however the effectiveness of existing policies is unknown. The project expects to identify impacts of key reforms on employment, re-training, income, savings and future retirement income and public pension receipt. The project will develop a new tax records-based dataset to facilitate future research on tax and welfare systems.Read moreRead less
Severe Malaria In Children In Papua New Guinea: A Longitudinal Study Of Pathophysiology, Management And Outcome
Funder
National Health and Medical Research Council
Funding Amount
$484,808.00
Summary
The features of severe infection in children living in tropical countries may not allow differentiation between malaria and bacterial-viral causes. This can create significant problems with deciding on appropriate management. In addition, the main complications of malaria such as coma, increased acid levels in the blood and anaemia are not well understood. We plan to characterise infections in Papua New Guinean children in detail and explore mechanisms behind important malarial complications.