Determining The Impacts Of Epigenetic Modifying Drugs On Germline Programming And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$863,918.00
Summary
New drugs have been developed that inhibit specific enzymes that regulate epigenetic pathways in cells. These pathways significantly affect growth and development in offspring and may represent a risk to future children of patients taking the drug. This project will determine these risks and provide data for developing clinical guidelines for safe use of the drugs.
Focus On The Uterus: Basic And Translational Research Strategies To Address Key Issues In Women’s Health. Fertility, Infertility, Endometrial And Pregnancy Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$1,085,790.00
Summary
My work focuses on the endometrium, the lining of the uterus, into which the embryo implants to establish pregnancy. When the endometrium does not function correctly, the woman is usually infertile. Other disorders of the endometrium include endometriosis, menstrual bleeding problems and cancer. My studies have defined the molecular basis for much endometrial dysfunction. I am now developing non-invasive tests for these problems and rationales for new treatments.
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
I am a perinatal physiologist who specializes in determining the factors that cause fetal and neonatal brain damage, and in devising treatments to prevent this for application in pregnant women and the neonate.
Hypospadias is one of the most common developmental defects in humans, yet over two thirds of the cases cannot be explained. Our recent studies using marsupials show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. This study will provide novel data on the interactions of the genes and hormones that will inform our understanding of this common developmental defect of male development
Therapeutic Potential Of Transforming Growth Factor-beta Proteins For The Diagnosis And Treatment Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$942,961.00
Summary
We discovered and manufactured a growth factor produced uniquely by the egg. We named this growth factor cumulin. It is a powerful regulator of ovarian function and egg quality. This project will study the basic mechanisms of how cumulin works in the ovary. We will then develop an assay to measure it as a biomarker of human egg quality and quantity. New approaches in fertility preservation for cancer survivors will be developed using cumulin.
Prevention Of Placental Oxidative Stress And Inflammation By Dietary Omega-3 Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Several pregnancy disorders that result in low birthweight involve aberrant function of the placenta. In this project we will examine one of the key mechanisms underlying placental dysfunction, namely oxidative stress, and determine whether its adverse effects can be limited by supplementation with dietary omega 3 fatty acids. The outcomes of this project will help guide future clinical studies on the possible beneficial effects of omega-3 fatty acids in pregnancy.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.