Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
The Fetal Response To Infection, With Particular Reference To Alterations Of Tryptophan Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$410,616.00
Summary
Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released f ....Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released from bacteria induce cells in the uterus and placenta to produce inflammatory chemicals that can damage the brain. In this project we propose the following model: 1), infection causes the release of substances from the uterus and placenta that disrupt the blood-brain barrier in the fetal brain; and, 2), infection alters the metabolism of the essential amino acid tryptophan in the fetus, causing greater production of metabolites that have toxic effects on the developing brain. We have preliminary evidence to support these two proposals. If the idea is proven correct, it should be possible to administer simple analogues of tryptophan to prevent the toxic metabolites of this amino acid from increasing in the fetus when either the mother or the uterus becomes infected. Because these substances can be given by mouth, this would allow a simple treatment to be developed for women at risk of infection, or who are already infected. This would be particularly useful wherever medical services and resources are limited, as for under-priviledged groups and in Third World countries.Read moreRead less
Impact Of Chronic Intrauterine Inflammation On Neurodevelopmental & Physiological Responses To Fetal Hypoxia.
Funder
National Health and Medical Research Council
Funding Amount
$280,750.00
Summary
Careful examination of records from hundreds of pregnancies has indicated that low-grade infection or inflammation within the uterus during pregnancy is associated with an increase in the likelihood that the newborn baby will suffer from cerebral palsy. This strong association suggests that inflammation during pregnancy can cause damage to the developing baby's brain. Similar studies have also identified an association betwen events that result in a lack of oxygen supply to the developing brain ....Careful examination of records from hundreds of pregnancies has indicated that low-grade infection or inflammation within the uterus during pregnancy is associated with an increase in the likelihood that the newborn baby will suffer from cerebral palsy. This strong association suggests that inflammation during pregnancy can cause damage to the developing baby's brain. Similar studies have also identified an association betwen events that result in a lack of oxygen supply to the developing brain and cerebral palsy. However the studies that have identified these associations are incapable of determining the mechanisms by which these factors affect brain development. Even though inflammation during pregnancy is common, and is often associated with diseases after birth, experimental studies of the effects of this type of inflammation on the wellbeing of the unborn baby have not been performed. Our research group has developed a unique experimental model, using sheep, which is particularly suitable for determining how inflammation and a lack of oxygen may affect the unborn baby and cause brain damage. By continuously giving a sterile bacterial cell wall preparation (endotoxin) into the amniotic fluid of pregnant sheep we can cause prolonged inflammation with characteristics that are similar to those that accompany inflammation during human pregnancy but different to other models of inflammation within the uterus. We intend to use our model to determine how prolonged inflammation and a lack of oxygen affect the well-being of the developing lamb before birth and how these factors affect brain development. Our proposed study will provide valuable information about how inflammation and a lack of oxygen interact to affect brain development. We expect that when inflammation is present the fetus becomes more vulnerable to the effects of a lack of oxygen, resulting in more severe brain damage occuring than when either factor is experienced alone.Read moreRead less