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
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.
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.
Regulation Of Progesterone Action In Human Parturition.
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Premature birth is the leading cause of neonatal death and sickness, and numbers are increasing due to our ignorance of the biology of labour. Progesterone maintains pregnancy and its withdrawal results in birth, but how this is achieved in humans is unknown. This project will determine the molecular mechanisms by which progesterone action is regulated during the transition from pregnancy to birth. This data will guide new strategies to prevent premature birth.
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
Rhythmicity And Synchronicity In Uterine Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$291,823.00
Summary
Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that ....Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that rhythmicity and synchronicity of uterine contractions are underpinned by store pacemaking. Second, we will probe the role of current spread between cells via gap junctions as a mechanism of recruitment and will examine whether accessory cells termed interstitial cells subserve a role in pacemaking. These cells are present within the uterine wall but their function is unknown. We will probe their ion channel properties in relation to pacemaking using patch clamp techniques. Third, we will examine the role of labour hormones, such as oxytocin, in augmenting uterine contractions via interaction with the Ca2+ store mechanism and cell recruitment. These studies will provide new and fundamental insights into uterine pacemaking, an outcome that should be of great significance to understanding and better controlling birth-associated complications such as preterm delivery and failure to progress.Read moreRead less
The Role And Regulation Of Phospholipase Isozymes In The Initiation Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$462,589.00
Summary
Being born too early is the most significant problem facing contemporary clinical obstetrics in the developed world. Preterm birth is the major cause of ill-health and death in newborns, accounting for 85% of all early infant deaths, not secondary to genetic abnormality. In Australia in 1998, more than 17,000 babies were born too early, of these over 10,000 suffered respiratory complications and 1300 died during the first 21 days of life. Even though the likelihood of a premature baby surviving ....Being born too early is the most significant problem facing contemporary clinical obstetrics in the developed world. Preterm birth is the major cause of ill-health and death in newborns, accounting for 85% of all early infant deaths, not secondary to genetic abnormality. In Australia in 1998, more than 17,000 babies were born too early, of these over 10,000 suffered respiratory complications and 1300 died during the first 21 days of life. Even though the likelihood of a premature baby surviving doubles for every two weeks that birth is delayed (between 23 and 28 weeks of gestation), currently there is no treatment available that reliably delays or prevents premature birth. In order to develop clinically useful treatments and improve pregnancy outcome and the well-being of our newborn, it is essential to understand the mechanisms that start the process of labour and delivery. Thus, the overall aim of this project is to increase our understanding of how human labour is initiated and to identify processes that may be manipulated to delay premature birth. In particular, this project focuses on the role and regulation, of what we believe is, a central and common pathway involved in triggering the birth process. This pathway is a known regulator of inflammatory process in the body. Intriguingly, the process of birth displays many of the hallmarks of an inflammatory reaction. Our pilot studies suggest that this pathway is involved in activation many of the events that occur at the time of birth and that further investigation of its role will provide valuable insights in to what triggers human birth. The specific aims of this project are (i) to develop a better understanding of the mechanisms that initiate human labour and (ii) to identify more effectively ways of prevent preterm birth.Read moreRead less
Control Of Uterine Contraction: Role Of Interstitial Cells
Funder
National Health and Medical Research Council
Funding Amount
$587,206.00
Summary
Being born premature may increase risk of below average IQ, poor performance at school and behavioural difficulties in the child, and increased obesity and blood pressure as an adult, predisposing to life long socio-economic disadvantage. We have come up with a new approach to understanding the control of uterine contraction, namely, that cells other than muscle cells, recently identified in the uterine wall, are essential for inducing forceful and orderly muscle cell contraction during labour.
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