Disrupted Neurosteroid Synthesis Mediates The Adverse Effects Of Prenatal Stress
Funder
National Health and Medical Research Council
Funding Amount
$695,973.00
Summary
Maternal anxiety and related stress in pregnancy influences the fetus causing developmental changes that adversely affect the offspring leading to behavioural problems in childhood. However, mechanisms which transfer maternal changes to the fetus are unclear. We propose that disruption of the fetal-placental neurosteroid system is a major link. We will identify the deficits in this system caused by maternal stress and then examine therapies to reverse these disruptions.
Cell-cell fusion is critical for the development and transport capacity of the placenta during pregnancy. Impairments in this process occur in pregnancy complications such as preeclampsia (PE). We have identified a novel pathway (LY6E) regulating placental cell-cell fusion which is also dysregulated in human pregnancies complicated by PE. In the current proposal we will investigate the mechanisms by which LY6E mediates cell-cell fusion and examine its role in the development of PE.
The Consequences Of Innate Immune Inflammatory Responses During Early Pregnancy And Their Effect On Reproductive Outcomes.
Funder
National Health and Medical Research Council
Funding Amount
$367,788.00
Summary
The mother's immune system can tolerate the growth of an ostensibly foreign fetus during pregnancy, yet remain vigilant to pathogenic challenge. We will investigate whether exposure to viral infections during early pregnancy leads to maternal and fetal inflammation which then impacts adversely on reproductive outcomes including fetal development and life-long health of offspring. Answers to these questions will contribute in designing effective interventions to limit the potential for detrimenta ....The mother's immune system can tolerate the growth of an ostensibly foreign fetus during pregnancy, yet remain vigilant to pathogenic challenge. We will investigate whether exposure to viral infections during early pregnancy leads to maternal and fetal inflammation which then impacts adversely on reproductive outcomes including fetal development and life-long health of offspring. Answers to these questions will contribute in designing effective interventions to limit the potential for detrimental outcomes.Read moreRead less
Improving The Fetal To Neonatal Transition In Compromised Newborns; Towards Better Outcomes For Babies Born Too Soon Or With Under-developed Lungs
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The birth of a compromised infant affects 13 million pregnancies worldwide annually and is the greatest cause of neonatal death, disability and chronic disease. I will identify mechanisms to greatly improve the fetal to neonatal transition in premature babies and babies with under-developed lungs. This research is urgently required to provide the necessary evidence to target interventions in the delivery room to reduce the short- and long-term burden of disease in compromised newborns.
Creatine Supplementation In Pregnancy: Utilising Cells’ “Built-In” Energy Buffering System
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Through pregnancy, the placenta transfers oxygen and nutrients from the mother to the baby. When a placenta doesn’t function properly a baby’s health is compromised. This can lead to morbidity or death. Creatine is the “back-up generator” of all cells and could help the failing placenta increase nutrient and oxygen delivery to the baby. This study will develop creatine as a potential new therapeutic, to improve the survival of babies of complicated pregnancies.
Novel Molecular Pathways Of The Placental Renin Angiotensin System In Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$323,524.00
Summary
Preeclampsia (PE) is a common and potentially life-threatening pregnancy disorder of pregnancy which originates in the early placenta. We will look into new interactions between molecules that determine how early cells establish a functioning placenta. Detection and early treatment of abnormal placental function can prevent PE before serious complications develop.
Effective Treatment Of Ureaplasma To Prevent Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$701,652.00
Summary
Premature births are often due to infection in the uterus by microorganisms named Ureaplasmas. Antibiotics given to the mother fails to eradicate them, probably because of poor passage of the drug across the placenta. This project asks if antibiotics should instead be given as a single injection into the amniotic fluid. Clinical studies will evaluate the frequency and types of Ureaplasmas in amniotic fluid. Studies with sheep will work out which antibiotic would be most effective and at which ro ....Premature births are often due to infection in the uterus by microorganisms named Ureaplasmas. Antibiotics given to the mother fails to eradicate them, probably because of poor passage of the drug across the placenta. This project asks if antibiotics should instead be given as a single injection into the amniotic fluid. Clinical studies will evaluate the frequency and types of Ureaplasmas in amniotic fluid. Studies with sheep will work out which antibiotic would be most effective and at which route and dose.Read moreRead less
Periconceptional Alcohol Exposure: Effects On The Embryo And Fetus And Disease Risk In Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
It is known that consuming large amounts of alcohol during pregnancy can have deleterious effects on fetal growth and development. Less is known about the effects of consumption of alcohol just around the time of conception. This project will use animal models to explore if alcohol can alter development of the very early embryo and whether this has long term consequences for the health of offspring after birth.
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.
DEVELOPMENT OF FOLDING IN THE FETAL CEREBRAL CORTEX – IDENTIFYING FUNDAMENTAL MECHANISMS AND THEIR SUSCEPTIBILITY TO DISRUPTION IN NORMAL AND ABNORMAL PREGNANCY
Funder
National Health and Medical Research Council
Funding Amount
$607,742.00
Summary
During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these importan ....During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these important processes.Read moreRead less