Defects of the internal and external genitalia are among the most common birth defects in babies (1 in 4,000 births) yet the aetiology in many cases is unclear. We will compare and contrast the mouse with a unique animal model the tammar wallaby to investigate the control of ovarian differentiation during early fetal and postnatal life. The gonad is unusual in that two completely different organs arise from the same precursor tissues, so that errors in development lead to intersexual phenotypes. ....Defects of the internal and external genitalia are among the most common birth defects in babies (1 in 4,000 births) yet the aetiology in many cases is unclear. We will compare and contrast the mouse with a unique animal model the tammar wallaby to investigate the control of ovarian differentiation during early fetal and postnatal life. The gonad is unusual in that two completely different organs arise from the same precursor tissues, so that errors in development lead to intersexual phenotypes. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutations. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. We will use comparative analysis and an inducible sex reversal system to understand the way gene expression and hence tissue differentiation is altered between male and female during the formation of the ovary versus the testis. This will inform us about the causes and consequences of normal and abnormal sexual development, infertility and gonadal malignancies.Read moreRead less
Analysis Of Gene Regulation In Disorders Of Sex Development
Funder
National Health and Medical Research Council
Funding Amount
$524,852.00
Summary
Disorders of Sex Development (DSD) are surprisingly common, however the majority of cases still cannot be explained. Our hypothesis is that a significant proportion of DSD is due to disturbed gene regulation. We will use state of the art methods to analyse the regulation of DSD genes. Our research will improve our knowledge of the regulation of genes that affect DSD and provide a diagnosis for DSD patients for whom the underlying cause is unknown. This in turn will improve clinical management.
Disorders of sex development (DSDs) are surprisingly common, and often result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. This research combines expertise in human molecular genetics, mouse developmental biology and protein chemistry to identify genes important for sex determination and development of the gonads, and discover how they contribute to DSD, in order to improve clinical care to patients with DSD.
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
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.
Development Of A Specific Activin Antagonist For Therapeutic Applications
Funder
National Health and Medical Research Council
Funding Amount
$504,287.00
Summary
Activin is a key regulator of homeostasis in several organs and tissues, including ovaries, testes, liver and skin, and alterations in activin�s activity can result in fibrosis, cachexia and cancer. In this grant we propose to develop a specific activin antagonist by modifying the activin A propeptide. This novel reagent could be used to promote liver growth in severe hepatic disease and prevent fibrosis in numerous tissues.
Defects in sexual development in the human embryo result in some of the most common forms of birth defects, which have profound physiological and psychosexual ramifications for the afflicted individuals. A fuller understanding of the causes of these defects may lead to improved counseling and perhaps also therapeutic possibilities. This project is aimed at finding and studying the genes that control whether an embryo develops as a male or a female, and the genes that are responsible for proper d ....Defects in sexual development in the human embryo result in some of the most common forms of birth defects, which have profound physiological and psychosexual ramifications for the afflicted individuals. A fuller understanding of the causes of these defects may lead to improved counseling and perhaps also therapeutic possibilities. This project is aimed at finding and studying the genes that control whether an embryo develops as a male or a female, and the genes that are responsible for proper development of the gonads, organs that control an individual's sexual development. It is thought that a genetic chain of events is important for gonadal development, and we aim to find the missing links of that chain and to work out how they fit together.Read moreRead less
Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$539,000.00
Summary
Disorders of sexual development are among the most common forms of birth defects in humans (1 in 4,000 births). Many other childhood conditions with this incidence warrant prenatal diagnosis or neonatal screening. These disorders often result in infertility, genital abnormalities and gender mis-assignment. Uncertainty about a child s gender at birth can be very traumatic physically and psychologically for the individual and family concerned. There are profound consequences in later life for the ....Disorders of sexual development are among the most common forms of birth defects in humans (1 in 4,000 births). Many other childhood conditions with this incidence warrant prenatal diagnosis or neonatal screening. These disorders often result in infertility, genital abnormalities and gender mis-assignment. Uncertainty about a child s gender at birth can be very traumatic physically and psychologically for the individual and family concerned. There are profound consequences in later life for the affected individual. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research project will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans.Read moreRead less