Role Of Endogenous Opioid Peptides In Endometrial Receptivity And Placentation
Funder
National Health and Medical Research Council
Funding Amount
$523,884.00
Summary
Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth w ....Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth weight are much more likely to develop a host of diseases including cardiovascular disease, diabetes and obestiy in adult life increasing the long term burden of health care support. Infertility is often due to the lack of uterine endometrial receptivity while the pregnancy complications arise from the reduced growth of the placenta and sub-optimal interactions between the mother's uterus and the growing placenta. Endometrial infertility, placental growth and interactions with the endometrium is stringently regulated by substances produced at the maternal endometrial- placental interface. To understand how infertility and pregnancy complications arise, develop diagnostic, monitoring and therapeutic tests it is critical to understand the roles played by these regulatory substances. We have novel data suggesting that small proteins known as endogenous opioids could be enchancing endometrial receptivity and the growth and development of the placenta. Interstingly these substances are closely related to exogenous opioids such as heroin and morphine. We will investigate the manner in which these substances regulate endometrial immune cell function, maintain the endometrial stromal cell bed in preparation for pregnancy and direct the growth and differentiation of the placenta. The findings will give novel insights into infertility, improve the success rates of in vitro fertilization, reduce maternal and neonatal complications of pregnancy.Read moreRead less
We have found that during infection a protein (called IDO) is made in cells lining arteries. IDO degrades tryptophan into kynurenine, which can open arteries, while blocking IDO increases blood pressure. We will now study the importance of this metabolic pathway in various diseases using mice with either absent or high levels of IDO, and also perform the first such studies in human blood vessels. We predict the research to have a tremendous impact on our understanding of cardiovascular diseases.
Treatment Of Cerebral Palsy - An Experimental Approach
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Cerebral palsy is characterised by disordered movement evident early in life leading to lifelong disability. The motor disorder arises from an abnormality within the white-matter of the brain that is non-progressive and is identifiable soon after birth. In humans and experimental models of fetal infection there is an increase in markers of inflammation. We will use induce ovine fetal infection and white matter injury to examine if anti-inflammatory treatments can prevent fetal brain damage.
Fetal Responses To Intra-uterine Inflammation And The Postnatal Pulmonary Consequences
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
There is increasing evidence that exposure of the unborn baby to infection and inflammation may be the cause of several important and disabling illnesses in later life, including long-term lung injury and brain damage. Hospital-based studies have shown that infants who go on to develop these diseases have signs of inflammation before, and soon after, birth. These studies in humans, however, have only shown associations between inflammation and later disease. Carefully controlled scientific exper ....There is increasing evidence that exposure of the unborn baby to infection and inflammation may be the cause of several important and disabling illnesses in later life, including long-term lung injury and brain damage. Hospital-based studies have shown that infants who go on to develop these diseases have signs of inflammation before, and soon after, birth. These studies in humans, however, have only shown associations between inflammation and later disease. Carefully controlled scientific experiments are required to show that inflammation actually causes damage and to allow us to find ways to prevent or cure the diseases that result from such injury. In 1998, using sheep, our research group discovered a way to produce inflammation in the fetus without endangering its wellbeing or causing early labour. The inflammation is caused by injecting a sterile bacterial cell wall preparation (endotoxin) into the amniotic fluid surrounding the fetus. Using this model, we have found that an episode of inflammation before birth profoundly increases lung maturity, thus increasing the chances of survival if premature birth occurs. Based on our information from humans, we expect that if these lambs are allowed to survive past the first few days after birth, they will go on to develop chronic lung disease, and perhaps brain damage. This study will answer vital questions about the events that occur in the uterus and the fetus during periods of inflammation, and will then determine the long-term consequences in the weeks following birth. We expect that these lambs will have changes which at first will increase their chances of survival after birth, to be followed by chronic disability due to lung and brain damage. If confirmed, this finding will allow us to find treatments which can be applied before birth to ensure that children are less likely to be born with these disabling illnesses.Read moreRead less
Antenatal Insulin-like Growth Factor-I And Perinatal Growth, Survival And Function Of The Growth Restricted Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$150,370.00
Summary
Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUG ....Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.Read moreRead less
Contribution Of Systemic Inflammatory Response To Brain Injury In Growth Restricted Newborns
Funder
National Health and Medical Research Council
Funding Amount
$363,388.00
Summary
Growth restriction during pregnancy can damage the baby’s brain and result in poor outcomes such as learning and attention difficulties and cerebral palsy. Currently there is no treatment available to prevent brain injury in these babies. This study will explore the role of inflammation and brain injury in the growth restricted baby. We will also examine whether a readily available and safe anti-inflammatory treatment can reduce or prevent brain injury following growth restriction.
Fetal Cardiovascular Development And The Impact Of Chronic Hypoxia And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$307,232.00
Summary
Low birth weight occurs in 7% of Australian babies and is associated with an increased risk of cardiovascular disease in adult life. Understanding the mechanisms underlying heart and blood vessel development in low birth weight babies will lead to improved identification and intervention in those individuals at risk of cardiovascular disease in adult life, improving heart health for Australians. Reducing cardiovascular disease will improve both quality and quantity of life for Australians.
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.
Roles Of PTHrP And Calcium In Mammary Function In Perinatal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Babies that are born small have significant problems around the time of birth and may have limited catch-up growth. A recently discovered protein known as PTHrP influences the nutrition of the growing newborn through breast milk. Because of its potential importance to small babies we intend to study this protein during and after pregnancy in rats and their pups. New treatments may emerge from the knowledge gained from these studies that may improve the growth and health of infants.