HtrA4-induced Endothelial Dysfunction In Early-onset Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$86,073.00
Summary
Preeclampsia (PE), a life-threatening disorder of pregnancy, is characterized by a sudden increase in blood pressure in association with wide-spread endothelial dysfunction. Placenta-derived factors are believed to cause PE development. Our recent studies have identified that HtrA4, a placenta-specific serine protease may contribute to endothelial dysfunction. This study will investigate the mechanisms of HtrA4-induced endothelial dysfunction.
Comparison Of Pregnancy Outcomes Following Transferring One Or Two Embryos In A Selected Group Of Infertility Patients.
Funder
National Health and Medical Research Council
Funding Amount
$120,302.00
Summary
Assisted reproductive technology (ART) deals with issues of fundamental importance to individuals involved, and society as a whole. Despite major advances, ART continues to be very costly in many regards. A major reason for this is the relatively low rate of pregnancy, which averages 25% per procedure. The common response to the problem of low pregnancy rates is to return several embryos to uterus. A dilemma associated with this strategy is the high risk of multiple pregnancy, which is associate ....Assisted reproductive technology (ART) deals with issues of fundamental importance to individuals involved, and society as a whole. Despite major advances, ART continues to be very costly in many regards. A major reason for this is the relatively low rate of pregnancy, which averages 25% per procedure. The common response to the problem of low pregnancy rates is to return several embryos to uterus. A dilemma associated with this strategy is the high risk of multiple pregnancy, which is associated with adverse consequences for mother and fetus(es). Compared to singleton births; fetal, neonatal, and perinatal mortality rates are 3-6 times higher in twins, and 5-15 times higher in multiple births of a higher order. Cerebral palsy rates among survivors are six times higher in twins and twenty times higher in triplets. The increase in the incidence of adverse outcomes related to multiple pregnancy has been well documented in ART. We propose a randomised controlled study to assess single embryo transfer (SET) compared to double embryo transfer (DET). Infertility women with a high risk of multiple pregnancy will be randomly allocated to receive one or two embryos, which is the usual treatment at present. We shall then examine the rates of single and multiple pregnancies, and the success of those pregnancies in this group of patients. Potential benefits to the community from this project are very substantial, as it has the capacity to substantially reduce the number of multiple births. Patients will also benefit by having more accurate information with which to make an informed choice during treatment.Read moreRead less
Implantation of an embryo into the uterus & development of a functional placenta are critical to initiate & continue a pregnancy. Implantation failure causes infertility and is a major bottle-neck in IVF. Placental insufficiency leads to pregnancy loss, under-developed fetuses & a life-threatening pregnancy-specific disease preeclampsia. This application will investigate how a woman’s uterus works for implantation and placental development, how to increase IVF success and diagnose & potentially ....Implantation of an embryo into the uterus & development of a functional placenta are critical to initiate & continue a pregnancy. Implantation failure causes infertility and is a major bottle-neck in IVF. Placental insufficiency leads to pregnancy loss, under-developed fetuses & a life-threatening pregnancy-specific disease preeclampsia. This application will investigate how a woman’s uterus works for implantation and placental development, how to increase IVF success and diagnose & potentially treat preeclampsia.Read moreRead less
The Mechanisms That Regulate The Onset Of Human Labour And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$528,170.00
Summary
Reproductive biologists still cannot explain the molecular mechanisms that govern human birth. This lack of knowledge prevents the development of better moitoring and treament of complications of labour and delivery. If we are to provide the best possible start to life and improve newborn health care delivery then we must: (1) better understand what triggers labour; (2) determine whether there are biomarkers that we can use to identify women at risk of early birth; and (3) identify new ways to d ....Reproductive biologists still cannot explain the molecular mechanisms that govern human birth. This lack of knowledge prevents the development of better moitoring and treament of complications of labour and delivery. If we are to provide the best possible start to life and improve newborn health care delivery then we must: (1) better understand what triggers labour; (2) determine whether there are biomarkers that we can use to identify women at risk of early birth; and (3) identify new ways to delay birth. This is the overall objective of this research project. In particular, this project focuses on how the multiple events needed to achieve a successful outcome to pregnancy are coordinated at the time of birth.Read moreRead less
P-glycoprotein: A New Player In The Placental Glucocorticoid Barrier
Funder
National Health and Medical Research Council
Funding Amount
$424,711.00
Summary
Adequate growth and development of the fetus are crucial for survival of the newborn. The placenta plays a central role in these processes, providing the fetus with appropriate nutrients and hormonal signals. The placenta also regulates the maternal-fetal passage of hormones, some of which have the capacity to limit fetal growth. These include glucocorticoid hormones from the mother's adrenal gland (eg cortisol) which are normally prevented from passing through the placenta to the fetus due to t ....Adequate growth and development of the fetus are crucial for survival of the newborn. The placenta plays a central role in these processes, providing the fetus with appropriate nutrients and hormonal signals. The placenta also regulates the maternal-fetal passage of hormones, some of which have the capacity to limit fetal growth. These include glucocorticoid hormones from the mother's adrenal gland (eg cortisol) which are normally prevented from passing through the placenta to the fetus due to the 'placental glucocorticoid barrier'. The primary focus of this proposal is the investigation of a potential new contributor to this barrier called P-glycoprotein (P-gp), recently shown to limit access of glucocorticoids to the brain. We propose that because the placenta expresses significant amounts of P-gp, it may help prevent maternal glucocorticoids from reaching the fetus and causing growth retardation. We will determine whether P-gp is a significant contributor to the placental glucocorticoid barrier, and measure how much P-gp is present in normal placentas throughout pregnancy. We will also assess whether there is less P-gp present in placentas of growth-retarded fetuses. Understanding how P-gp affects the passage of glucocorticoids across the placenta could help to treat certain cases of fetal growth retardation.Read moreRead less
Interleukin 11 And Leukemia Inhibitory Factor: Pivotal Regulators Of Uterine Receptivity And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Interleukin (IL)-11 and leukemia inhibitory factor (LIF) are critical for embryo implantation in mice but their mechanisms of action in women are not well defined. We will define their roles in the establishment of pregnancy and provide new critical information on their potential as targets for diagnostic and therapeutic tools for infertility and major diseases associated with pregnancy.
Interstitially Invasive Trophoblast Of The Murine Placenta: Developmental Origins, Functions And Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$369,717.00
Summary
Due to the obvious limitations to studying human pregnancy, the mouse has become a valuable model. However, invasion of the placenta into the uterine wall and vasculature, critical for successful pregnancy, is poorly understood in the mouse. The aims of the proposal are designed to gain a better understanding of these processes in mice and will provide a more accurate model system to study serious pregnancy complications resulting from abnormal placental invasion, such as preeclampsia.
Mechanisms Of Escape From Progesterone-induced Suppression: Role In Normal And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Prematurity caused by preterm birth is the leading cause of death and disease among newborns in Australia. Here we will define how the length of pregnancy is determined by the opposing actions of progesterone, which maintains pregnancy, and prostaglandins, which induce labour. We will demonstrate the mechanism by which the actions of the two hormones are balanced in normal pregnancy and disrupted in preterm labour. We will show that preterm birth can be prevented by correcting the disorder.
Understanding Immune Tolerance In Pregnancy To Discover A New Intervention For The Treatment Of Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$492,202.00
Summary
Pre-eclampsia is a common complication of pregnancy. Women who develop pre-eclampsia experience high blood pressure, swelling and lose protein in the urine. There is no treatment for pre-eclampsia other than delivery of the baby. Pre-eclampsia has risks for the mother and the baby. This research will discover whether generalised inflammation in the mother is a cause of pre-eclampsia and will evaluate the role of a novel treatment for its potential to prevent this life threatening condition.
Metabolic And Molecular Determinants Of Embryo Viability
Funder
National Health and Medical Research Council
Funding Amount
$551,321.00
Summary
We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data dem ....We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data demonstrating that exposure of embryos to physiological perturbations alters fetal development, similarly to that occurring in nutrient restriction during pregnancy. Furthermore, there is data from IVF-derived children that their birth-weight is lower than expected, possibly due to the conditions used for conception in the laboratory. How does the response by eggs and embryos, at the time of conception, affect subsequent development? There has been some focus on changes to DNA that are not related to mutations, but structural changes in the DNA that alters gene expression. We call this epigenetics and epigenetic changes are found in embryos, including human embryos following IVF. However, no one knows how such epigenetic changes occur as a result of this stress response by the egg or embryo. Our proposal is to determine the mechanism of how epigenetic alterations take place in eggs and embryos. Our theory is that the mitochondria, the energy producing packages within all cells, are sending signals to the embryo's nucleus. When the egg or embryo finds itself in adverse conditions, the signals change as a result of changes in the energy balance. This in turn changes the activity of enzymes in the nucleus that regulates DNA structure. If we can prove that this relationship occurs, then we can assess these changes in human embryos that are excess to a patient's requirements and learn if programming takes place in human embryos.Read moreRead less