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.
Perinatal Stress Leads To Neurosteroid Deficits And Adverse Behavioural Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$1,198,042.00
Summary
This grant will examine the effect of psychosocial stress experienced after birth on the production and regulation of steroid hormones in the brain of newborn animals. The work will investigate how stress changes the levels these brain steroids and sensitivity to them and if these effects are remain into adulthood. The studies will then determine if these changes lead to adolescent behaviour disorders. The effectiveness of steroid therapies in treating these disorders will also be determined.
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.
PROTECTING THE PRETERM FETAL BRAIN FROM HYPOXIA AND INFECTION: A HEALTHY START TO LIFE.
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. In recent years it has become evident that infections in the mother may be linked to both premature bi ....Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. In recent years it has become evident that infections in the mother may be linked to both premature birth and brain damage. It has been proposed that certain chemicals (cytokines), which are released during an infection, can cross the placenta to the fetus causing inflammatory changes that lead to brain damage. We have shown that an inflammatory inducing chemical (bacterial endotoxin) administered to immature fetal sheep induces brain damage similar to that seen in cerebral palsy. This provides an excellent model for testing agents that are known to block the action of cytokines and other markers of inflammation; currently there is no effective strategy for the treatment or prevention of hypoxia and inflammatory induced injury of the brain partly due to our ignorance about how and when the damage is occurring. We will test the effects of two chemicals; N-acetyl cysteine, which is known to block the generation of inflammatory cytokines, and the naturally occurring glycoprotein erythropoietin, which prevents death of neurons (apoptosis). We hope that by blocking these pathways we may be able to prevent brain injury from occurring when the immature fetus is exposed to an infection during gestation. We expect that this project will provide important novel information that helps us to understand how infection in the mother can cause brain injury in the fetus and provide a new approach for strategies to prevent or treat brain injury.Read moreRead less
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.
LIFECYCLE - Early Life Stressors And LifeCycle Health
Funder
National Health and Medical Research Council
Funding Amount
$453,811.00
Summary
Early in life is a period of time during which we can institute changes that can have long lasting benefits for asthma, obesity, diabetes mellitus and mental and cardiovascular health. The current project, LIFECYCLE is a cooperative project with a combined total of a quarter of a million participants, which will be the definitive study to determine, which early life events should be modified for improving health trajectories throughout life.
Intergenerational Transmission Of Gender-specific Metabolic Disease For Offspring Born Small: Maternal, Paternal And Embryonic Roles
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
This proposal addresses the underlying metabolic health consequences of poor embryo and growth of the baby across generations. We will define mechanisms by which a poor functioning placenta during a rat mother’s pregnancy programs her offspring born small to transmit gender-specific diseases to the next generation. We will identify mechanistic pathways involved, specifically the relative contributions of maternal and paternal germ lines and adverse maternal adaptations to pregnancy for females b ....This proposal addresses the underlying metabolic health consequences of poor embryo and growth of the baby across generations. We will define mechanisms by which a poor functioning placenta during a rat mother’s pregnancy programs her offspring born small to transmit gender-specific diseases to the next generation. We will identify mechanistic pathways involved, specifically the relative contributions of maternal and paternal germ lines and adverse maternal adaptations to pregnancy for females born small.Read moreRead less
The Consequences Of Innate Anti-viral Effector Responses On Reproductive Outcomes In Placental Mammals
Funder
National Health and Medical Research Council
Funding Amount
$328,060.00
Summary
The mother's immune system can tolerate the growth of an ostensibly foreign fetus during pregnancy. We will investigate whether exposure to viral infections either just before or during pregnancy can result in reduced fertility and whether it may affect fetal growth and development. These results will contribute in designing effective interventions to limit any potential detrimental outcomes.
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.