Gestational diabetes (GDM) is a common complication of pregnancy with significant consequences. Early identification and lifestyle intervention can prevent GDM, but the best early screening test is unknown. Our primary aim is to validate our first trimester screening test for GDM in a large multi-ethnic cohort to accurately predict high-risk women and intervene early, preventing GDM onset and improving pregnancy outcomes, including long-term risk of obesity in the offspring.
Pre-eclampsia is a serious medical condition affecting 5% of pregnancies and resulting in significant mortality and morbidity for mothers and babies. As yet there is no acceptable test capable of detecting pre-eclampsia in early pregnancy and diagnosis is made when symptoms and signs are manifest and management options are limited to early delivery. This project is designed to assess the ability of a blood screening test to detect pre-eclampsia in early pregnancy to enable for early intervention ....Pre-eclampsia is a serious medical condition affecting 5% of pregnancies and resulting in significant mortality and morbidity for mothers and babies. As yet there is no acceptable test capable of detecting pre-eclampsia in early pregnancy and diagnosis is made when symptoms and signs are manifest and management options are limited to early delivery. This project is designed to assess the ability of a blood screening test to detect pre-eclampsia in early pregnancy to enable for early interventions and preventative management to be implemented.Read moreRead less
Generational And Developmental Pathways Of Childhood And Adolescent Obesity: A Three Generation Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$1,281,100.00
Summary
There are no community-based follow-up (FU) studies of three generations able to examine the impact of earlier generational factors on the developmental pathways of obesity in third generation. The Mater-University of Queensland Study of Pregnancy (MUSP) cohort now has data covering the grandmothers' (GI) reproductive life course and a FU of their children (GII) into adulthood. We now propose a new study of the "children-of-the-children" who are the grandchildren (GIII) of GI and children of GII
A Novel Interaction Between The Immune And Vascular Systems In Early-onset Preeclampsia; An Opportunity For New Treatments?
Funder
National Health and Medical Research Council
Funding Amount
$921,623.00
Summary
Preeclampsia is a pregnancy complication that leads to poor birth outcomes and elevated lifelong cardiovascular disease risk in 4 million women each year. It has no cure and treatments are limited because the causal mechanisms are not understood. We have identified a specialised immune cell in the mother's blood that assists blood vessels to function properly in pregnancy. We will assess whether interventions to enhance these cells can improve poor blood vessel function and pregnancy outcomes.
Cohesin: Role In Germ Cell Chromosomal Segregation
Funder
National Health and Medical Research Council
Funding Amount
$435,526.00
Summary
At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related gen ....At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related genes, called Rec8 and Rad21, which we recently discovered in humans and mice. Due to that these genes are essential for chromosome separation in other species and they exists in species as diverse as yeast and humans, they may be responsible for accurate separation of chromosomes in germ cells in mammals. In this proposal, we will determine the role(s) of these molecules in controlling proper chromosome segregation by loss-of-function studies in genetically engineered mice lacking Rec8 and Rad21 genes. By analyzing the chromosomal abnormalities of the cells from these animals, we will gain critical information about the nature of chromosome partitioning disorders in humans.Read moreRead less
Relaxin Signalling In The Endometrium And The Regulation Of Early Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$466,125.00
Summary
Relaxin is a hormone, that is made in the ovary and the uterus, and plays a very important role in supporting the growth and development of the uterus so that the young embryo can implant properly. In fact, early pregnancy loss is associated with altered levels of relaxin in the blood. Very little is known about how relaxin works in the uterus. This project aims to address this important function, and makes use of cultured uterine cells prepared from tissues taken from women undergoing hysterect ....Relaxin is a hormone, that is made in the ovary and the uterus, and plays a very important role in supporting the growth and development of the uterus so that the young embryo can implant properly. In fact, early pregnancy loss is associated with altered levels of relaxin in the blood. Very little is known about how relaxin works in the uterus. This project aims to address this important function, and makes use of cultured uterine cells prepared from tissues taken from women undergoing hysterectomy for fibroids or similar illnesses. When these cells are grown in culture, we can mimic in vitro many of the events that occur in early pregnancy, causing the cells to differentiate and grow just as they would in vivo. Relaxin appears to exert its important effects on these cells by causing the concentration of the second messenger cAMP in the so-called stromal cells to increase greatly and in a sustained manner. It is this cAMP which is then responsible for many of the changes which are essential for healthy pregnancy. A knowledge of the molecular mechanisms behind these effects would help us firstly to understand how the uterus becomes receptive to an implanting embryo, and may explain why some women lose their babies in early pregnancy, or develop some of the negative symptoms associated with placental development such as growth restriction and preeclampsia. Relaxin appears to stimulate cells through the mediation of a new type of cell surface receptor, called LGR7. Whilst structurally this receptor looks like those for many other hormones, belonging to the group of so-called G-protein coupled receptors, it does not behave like these in natural uterine cells. Instead it appears to make use of completely new signaling pathways inside the cells. This project aims to unravel and understand these new pathways, thus providing information not only of importance for diagnosis and treatment of early pregnancy problems, but also of relevance for all other similar receptors.Read moreRead less
GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Epigenetic Programming Of The Hypothalmo-Pituitary-Adrenal Axis
Funder
National Health and Medical Research Council
Funding Amount
$550,951.00
Summary
It has been shown that the pattern of nutrition in early pregnancy is important in determining the subsequent health of the fetus and newborn. Interestingly, the nutritional environment of the early embryo, when nutrient demands are minimal has been shown to be important in determining the development of the capacity of the fetus to respond to stress in the womb and the timing of delivery. This proposal seeks to understand the mechanisms that underlie these responses.