Oxygen, Oxidative Phosphorylation And Regulation Of Embryo Development.
Funder
National Health and Medical Research Council
Funding Amount
$141,096.00
Summary
There is concern that human infertility treatment requiring the growth of embryos in the laboratory, as applied in human IVF, may cause problems during fetal development or even possibly lead to health problems much later in life as an adult. In particular, many clinics are now growing human embryos outside the body for several days longer (to select the best embryos for transfer) than what occurred a decade ago. This concern is based on the evidence that the environment in which an embryo grows ....There is concern that human infertility treatment requiring the growth of embryos in the laboratory, as applied in human IVF, may cause problems during fetal development or even possibly lead to health problems much later in life as an adult. In particular, many clinics are now growing human embryos outside the body for several days longer (to select the best embryos for transfer) than what occurred a decade ago. This concern is based on the evidence that the environment in which an embryo grows in has an impact on the way in which some genes are switched on and off. Normal on-off switching at appropriate times during early development should lead to healthy offspring. Failure to turn off or on, or inappropriate timing, may lead to consequences that manifest themselves later in development. We believe that oxygen concentration and the activity of mitochondria, the organelles of cells that converts oxygen into energy, are key regulators in turning on and off genes during early embryo development. This is because we have shown that, in embryos of a species that is metabolically similar to the human embryo, oxygen concentration and mitochondria activity need to change as the embryo grows for optimal development in the laboratory. In other mammalian cells, oxygen and mitochondria activity are known to turn on or off several particular genes, known as transcription factors. Transcription factors are genes which regulate other genes. Therefore, transcription factors are good candidates as regulators of early embryo development. The present project aims to determine if factors such as changing oxygen concentration and mitochondria activity during laboratory growth of embryos affects the way in which these transcription factors turn on and off. If we find this is true, the way in which human embryos are grown in the laboratory needs to be examined carefully to minimize the risk of possible long-term consequences to the resulting fetus.Read moreRead less
Identification Of Factors Essential For Oocyte Viability
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Approximately 2% Australia children are now conceived using in vitro fertilisation technologies, allowing infertile couples to bear their own children. However, a major consequence of IVF techniques is multiple pregnancies (i.e. twins and triplets) which is a major health risk to mothers and their infants. Furthemore, IVF increases birth defects, which are mostly attributed to the increased multiple pregnancies, but is also observed in pregnancies involving a single infant. It is essential that ....Approximately 2% Australia children are now conceived using in vitro fertilisation technologies, allowing infertile couples to bear their own children. However, a major consequence of IVF techniques is multiple pregnancies (i.e. twins and triplets) which is a major health risk to mothers and their infants. Furthemore, IVF increases birth defects, which are mostly attributed to the increased multiple pregnancies, but is also observed in pregnancies involving a single infant. It is essential that IVF techniques are developed that enables the transfer of a single embryo to the mother resulting in the birth of a single healthy baby, without the ethical concerns of surplus embryo disposal. Women receiving IVF are required to adminster hormones that stimulate the eggs in their ovaries to mature to the point where they can be fertilised by their partner's sperm. These hormones, called gonadotrophins, override the body's own ovarian stimulating system and cause many eggs to mature and be collected for fertilisation, instead of normally just one. In this way, the best embryo(s) can be selected for transfer back to the mother, and other embryos can be frozen and stored for later use. However, large doses of gonadotrophins has consequences. They can be dangerous to some patients who are sensitive to their potency, and stimulate a massive response. They also reduce the quality of eggs and subsequent embryos, which reduces the chances of a pregnancy. All this can be avoided if eggs can be collected from ovaries in an immature state and maturation achieved in the laboratory. However, although attempted, this has not been a successful technique, primarily because we don't understand the process of human egg maturation. Our research will investigate the biochemistry, physiology and genetics of non-human eggs and embryos resulting from eggs that are grown and matured in the laboratory, to develop techniques for the successful maturation of human eggs in the laboratory.Read moreRead less
Translating New Therapeutics And Diagnostics For Major Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
My research is focussed on tackling major complications of pregnancy that are a threat to the lives of both mother’s and babies. We are developing new drug treatments for ectopic pregnancy (a dangerous condition where the pregnancy implants in the Fallopian tube), and preeclampsia (a condition where toxins leak out of the placenta into mum's blood, and can seriously injure many of mum's major organs). We are also generating a blood test that may help women avoid the tragedy of a stillbirth.
Prediction And Prevention Of Spontaneous Preterm Birth: An Individual Participant Data Meta-Analysis Comprising Of Prognostic And Therapeutic Data
Funder
National Health and Medical Research Council
Funding Amount
$1,118,718.00
Summary
Spontaneous preterm birth is an important issue in obstetric care. Since potential treatments (pessary, progesterone) are available, accurate prediction is of imminent importance. We have established a collaborative network of >100 investigators (IPPIC-2) involved in primary studies with data on more than 1.2 milli women. We will estimate the value of individual clinical, biochemical and ultrasound markers for predicting preterm birth, and integrate that with therapeutic interventions.
Development Of Vinorelbine As A Tablet Based Therapy To Cure Ectopic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$361,594.00
Summary
Ectopic pregnancies occur if the pregnancy implants in the Fallopian tube. They can be deadly and most are treated surgically. We will examine the exciting possibility that instead of surgery, ectopic pregnancies may be cured with a tablet taken just once. We will perform laboratory studies and a clinical trial, giving vinorelbine to women with ectopic pregnancies.
Targeting The Anti-angiogenic Factors Of Preeclampsia: Soluble Endoglin And SFlt1
Funder
National Health and Medical Research Council
Funding Amount
$447,024.00
Summary
Preeclampsia is a severe disease of pregnancy - the placenta releases toxins in to mum's bloodstream that circulate her body and damage her organs. As there are no efficacious treatments, clinicians are forced to deliver babies irrespective of gestation. Although the two toxins of preeclampsia have been identified, little is known about their regulation. This project aims to elucidate the regulation of these toxins and design therapeutics that can prevent their release in the clinic.
Most pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction and stillbirth, stem from poor development of the placenta early in pregnancy. Restricted fetal growth in the uterus increases the babies risk of cardiovascular and other disorders in later life. This research will investigate whether Corin, an enzyme discovered in the heart, helps the mothers uterus prepare for pregnancy. Disruptions in Corin production during early pregnancy is likely to be involved in ....Most pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction and stillbirth, stem from poor development of the placenta early in pregnancy. Restricted fetal growth in the uterus increases the babies risk of cardiovascular and other disorders in later life. This research will investigate whether Corin, an enzyme discovered in the heart, helps the mothers uterus prepare for pregnancy. Disruptions in Corin production during early pregnancy is likely to be involved in major pregnancy complications and loss.Read moreRead less
Developing A Screening Test To Identify Women At Risk Of Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$1,119,284.00
Summary
Preeclampsia is a serious complication of pregnancy for which there is currently no cure and no way to accurately predict women at risk. Using large collections of human blood samples, we will screen for novel proteins within pregnant women's blood. We will then use artificial intelligence to select the best biomarkers and combine them with clinical information to develop a multi-marker blood test to predict women at risk.
Combination Methotrexate And Gefitinib To Cure Ectopic Pregnancies: Phase I-II Clinical Trials
Funder
National Health and Medical Research Council
Funding Amount
$235,875.00
Summary
Ectopic pregnancies are dangerous emergencies that can cause fatal bleeding. Most require surgery. We plan to test a novel medication-based treatment that could be used to cure most ectopics. If successful, it could revolutionise current management.
Soluble Endoglin In The Pathogenesis Of Preeclampsia: Investigation Of Mechanisms And The Development Of Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$572,733.00
Summary
Preeclampsia is a severe disease of pregnancy. As the pathogenesis is poorly understood, the only treatment is for clinicians to deliver babies irrespective of gestation. We have identified MMP-14 as the molecular scissors that release soluble endoglin from placenta, a toxin centrally responsible for severe preeclampsia. In this project we aim to further investigate the mechanisms governing soluble endoglin release and to begin developing a potential therapeutic for use in the clinic.