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.
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 seek the knowledge required to improve prevention, diagnosis and therapy for men with testicular pathologies by studying what controls early sperm development. My research will delineate how cellular signalling molecules lay the foundation for adult fertility, using animal studies, cell culture and clinical samples. Testis samples from testicular cancer patients will be used to test interventions that may kill tumour cells or offer a therapeutic option to men with impaired spermatogenesis.
Defining The Role Of Activin C In Gonadal And Adrenal Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$441,511.00
Summary
Activins are members of the inhibin/TGF_ superfamily of growth and differentiation factors. Our published work implicates one of them, activin-_C as a regulator of activin A synthesis and/or its action. To test our hypothesis we will cross activin-_C over-expressing mice (ActC++ ) with inhibin a subunit knock-out mice (_-KO) that develop gonadal and adrenal tumourigenesis and is caused by increased activin A. We predict that if correct, we will prevent or delay reproductive and adrenal tumourige ....Activins are members of the inhibin/TGF_ superfamily of growth and differentiation factors. Our published work implicates one of them, activin-_C as a regulator of activin A synthesis and/or its action. To test our hypothesis we will cross activin-_C over-expressing mice (ActC++ ) with inhibin a subunit knock-out mice (_-KO) that develop gonadal and adrenal tumourigenesis and is caused by increased activin A. We predict that if correct, we will prevent or delay reproductive and adrenal tumourigenesis and prolong survival.Read moreRead less
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.
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
Persistent Chlyamdial Infection In The Testes : Development Of A Successful Vaccine Strategy For Males
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Males are a reservoir of infection and novel vaccine approaches to control Chlamydia infections in young men are needed urgently. This study will be essential for the development of interventions to control infection and will inform strategies for manipulating the immune system within the male reproductive tract that may be applied to other sexually transmitted pathogens. The studies will benefit the health and welfare of the Australian people under National Research Priority 2, promoting and ma ....Males are a reservoir of infection and novel vaccine approaches to control Chlamydia infections in young men are needed urgently. This study will be essential for the development of interventions to control infection and will inform strategies for manipulating the immune system within the male reproductive tract that may be applied to other sexually transmitted pathogens. The studies will benefit the health and welfare of the Australian people under National Research Priority 2, promoting and maintaining good health and a healthy start to life.Read moreRead less
I am a clinician-scientist with a focus on basic and translational research in male reproductive physiology and health disorders, notably infertility, contraception and androgen action.