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.
A man's reproductive health and fertility is affected by processes that occur long before adulthood. The testis and sperm precursor cells first form in the fetus and then grow until the time of puberty, when the upper limit for sperm production is set. This project studies how one key signaling molecule, activin, helps establish normal testicular architecture and drives maturation of sperm precursor cells, and how it contributes to aberrent function in men with testicular cancer.
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.
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
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
ATR-X Syndrome: Role Of ATRX In Testicular Growth And Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$650,881.00
Summary
Infertility is surprisingly common and affects 1 in 20 Australian men. Testosterone and its receptor, the androgen receptor, are well known to be essential for spermatogenesis and fertility. We have identified an important regulator protein (ATRX) of androgen receptor activity and show that loss of function of ATRX in testes of mice leads to spermatogenesis defects. Identifying the molecular action of ATRX will lead to a better understanding of the underlying causes of infertility in men.
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
Male fertility requires sufficient production of healthy sperm in the testis. This project builds on our discovery that testicular cells communicate via the wnt family of proteins during sperm development, and that interruption of their activities reduces fertility in mice. We propose to use mouse models to study the precise steps in sperm production affected by Wnt signalling and how it works.
Growth Factors And Regulatory Genes Controlling Male Spermatogonial Proliferation And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$354,536.00
Summary
In newborn and prepubertal boys the testis contains germ cells which are at a premature stage of development and very suseptible to degeneration especially if the testes fail to descend to the scrotum. The molecules which are responsible for the health of these germ cells have been unknown and only recently the way has been opened for direct study of these factors. This has been made possible by a new assay, developed in our labarotory, in which we can grow these germ cells under defined conditi ....In newborn and prepubertal boys the testis contains germ cells which are at a premature stage of development and very suseptible to degeneration especially if the testes fail to descend to the scrotum. The molecules which are responsible for the health of these germ cells have been unknown and only recently the way has been opened for direct study of these factors. This has been made possible by a new assay, developed in our labarotory, in which we can grow these germ cells under defined conditions. This step forward has highlighted some areas of knowledge which need further research such as identification of the processes which stimulate gonocytes to grow and divide. We need to test growth factors, somatic cell factors and also isolate new genes which are associated with germ cells and their growth. This knowledge will have outcomes in two major areas. First, the new findings could be applied to treatment of infertility resulting from undescended testes in which a stimulus could be given to make the germ cells grow again. Second, work in developing longer term culture of germ cells coupled with introduction of mutations will enable us to make mutant mice with a specific gene abnormality, similar to transgenic or gene knockout mice. This technological development would prove less expensive and time consuming with more reproducible and direct outcomes. Mutant mouse technology is a powerful tool to determine the effects of individual genes in the whole animal (mouse).Read moreRead less