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.
Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian c ....Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. An understanding of the way gene expression and hence tissue differentiation is altered after sex reversal will inform us about the causes and consequences of normal and abnormal sexual development, gonadal malignancies and infertility. The gonad is unusual in that two completely different organs can arise from an essentially identical primordium, so that errors in development lead to intersexual phenotypes. We will use our new experimental animal model to clarify these processes.Read moreRead less
Roles Of TGFbeta Receptor TGFBR3 (Betaglycan) In Testis Development
Funder
National Health and Medical Research Council
Funding Amount
$332,660.00
Summary
Diseases of the reproductive tract are major health issues. At lease 1 in 100 live births display some sort of gonadal defects. Later in adulthood, one in six couples are affected by infertility, and cancers of the reproductive tract which result in a significant number of deaths each year. This project focuses on understanding the role of the transformation growth factor beta receptor3 (Tgfbr3) in the embryonic and neonatal testis and its impact on adult male reproductive capacities and health.
I am a reproductive biologist, studying how the environment, both in vivo and in vitro, interacts with oocytes and early embryos in determining both their short and long-term development, with specific interests in application to clinical infertility treatment.
Neuroendocrine Mechanisms By Which Leptin Regulates Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not k ....The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not known. Leptin is a hormone that is produced by fat and acts on the brain. This appears to be one of the means by which the reproductive system is regulated. Leptin also regulates food intake and other brain processes. Leptin acts on specific cell types in the brain. Some of these may have dual function to regulated appetite as well as reproduction. The present proposal is for work to determine mechanisms within the brain that are altered by leptin. We will also determine which specific mechanisms relate to the regulation of gonadotropin releasing hormone. The work will provide information on how putative appetite regulators might affect the reproductive axis. Such work will provide a platform for design of pharmaceutical means to manipulate the reproductive axis and will impact on the design of drugs that regulate obesity. It is possible that drugs that developed to control obesity may affect the reproductive axis and the project will identify these.Read moreRead less
A Novel Procedure For Efficacious Gonadotrophin-free Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
Infertility is common and is associated with health risks and is expensive. Using laboratory animals, we have developed a unique procedure, which has comparable success rates to IVF but crucially, it eliminates the need for ovarian hormone therapy used in IVF. A clinical trial using this method has started in Brussels and in this project we will examine cells from that trial and from animals to investigate the underlying mechanisms to enable safe and rapid clinical implementation.
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
Testis To Ovary: Hormonal Control Of Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$803,379.00
Summary
We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide f ....We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide formation of the ovary.Read moreRead less