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.
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
Copy Number Analysis Of Patients With Gonadal Abnormalities Using High Density Microarrays And MLPA
Funder
National Health and Medical Research Council
Funding Amount
$311,187.00
Summary
Congenital conditions in which development of the gonads or anatomical sex is abnormal are surprisingly common. The underlying cause of these problems is most often the failure of genes responsible for proper development of testes or ovaries. Only a small proportion of patients can be explained by mutations in known gonad determining genes. We will analyse DNA from these patients on very high density microarrays to identify new genes that cause abnormalities in testis and ovary development.
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
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
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
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
Genetics Of Intersex: Antagonism Between Male And Female Pathways During Gonadal Development
Funder
National Health and Medical Research Council
Funding Amount
$567,760.00
Summary
Disorders of sex Development (DSD) are congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Estimates suggest that between 1-100 and 1-300 live birth have DSD; however, the underlying genetic defect is unknown in 80% of cases. Generally, the fate of the gonad, testis or ovary, is determined by the balanced action of male (SRY) and female (Wnt- b-catenin) genes. How do these genes oppose each other? Is this antagonism deregulated in DSD patients?
Impairment of virilisation is one of the most common developmental defects in humans, yet over half the cases cannot be explained by our current knowledge. Studies of these processes is hindered because in most mammals virilisation occurs in the early fetus. Our recent studies using marsupials, where virilisation occurs after birth show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. We will conduct experiments using tammar ....Impairment of virilisation is one of the most common developmental defects in humans, yet over half the cases cannot be explained by our current knowledge. Studies of these processes is hindered because in most mammals virilisation occurs in the early fetus. Our recent studies using marsupials, where virilisation occurs after birth show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. We will conduct experiments using tammar wallabies and rabbits, to test 3 hypotheses about 5-alpha-androstanediol and specific enzymes in the developing reproductive tissues that either convert this hormone to active and inactive forms. The results of these experiments will direct testing for corresponding gene mutations in our collection of over 200 specimens from patients with defects of virilisation (pseudohemaphroditism) whose causes are still unknown. It is our expectation that the findings in these studies will provide insight not only into the pathways by which testicular hormones masculinize the developing male, but will also explain instances of male pseudohemaphroditism of unknown aetiology in humans.Read moreRead less