Germ Cell Development In The Postnatal Testis: The Key To Early Surgery To Prevent Infertility And Malignancy In Cryptorchidism
Funder
National Health and Medical Research Council
Funding Amount
$725,326.00
Summary
The germ cells have been studied very extensively before birth or after puberty, but little is known about what happens shortly after birth. In children with undescended testes, early germ cell development is deranged, and this may be the key to find the right time for surgery to prevent subsequent infertility and risk of cancer. This project proposes some novel hypotheses to explain this and the studies aim to obtain the evidence to support surgery in the first 3-6 months of life..
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.
Postnatal Germ Cells Are Controlled By FSH During 'minipuberty' At 3-6 Months, And Deranged By Cryptorchidism To Cause Seminoma And Infertility
Funder
National Health and Medical Research Council
Funding Amount
$813,739.00
Summary
This study will investigate the exciting possibility that the risk of cancer and infertility in adulthood in infants born with undescended testes might be obviated by understanding how primitive sperm cells behave in the postnatal testis. The study will define the key changes to the primitive sperm cells, including their timing and control by hormones, so surgery is done at the right time +/-accessory hormone treatment to optimise future sperm function for babies with undescended testes.
I am a cell biologist investigating how cells in the developing testis communicate to set the stage for normal sperm production in the adult. My studies address what goes wrong in certain clinical conditions including testicular cancer, and our findings a
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.
Activin Control Of The Male Germline For Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$915,786.00
Summary
The growth factor activin provides key signals in embryonic and infant testes to coordinate development of male germline cells into sperm. This project tests how activin controls genetic stability when the human testis is vulnerable to forming germline cells that become tumours in young men. We will study how activin acts to allow sperm stem cells to multiply and develop in sufficient numbers for adult fertility.
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.
Disorders Of Gonadal Development: Molecular Approaches To Improved Patient Care
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
We will use new genomic technologies to identify the genetic causes of disorders of sex development (DSD), a common and often distressing class of birth defect. Knowing the molecular lesion will take the guesswork out of diagnosis and treatment of DSD children. We will also exploit a new discovery to develop new means of rapid, cost-effective, non-invasive diagnosis and therapy for testicular cancer, the commonest form of cancer in men under 30.