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.
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.
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
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.
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.
Prenatal Origins And Health Outcomes Of Male Reproductive Congenital Anomalies Diagnosed At Birth And Testicular Cancer In Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$234,343.00
Summary
There is growing concern in increasing male reproductive congenital anomalies diagnosed at birth & testicular cancer in adulthood. Research suggests these conditions share a common origin due to disruption in the release of male hormones in early pregnancy. This study will use a novel method of record-linkage to investigate maternal and infant risk factors and their combined effect on male reproductive disorders at birth and later in life; & assess long-term health and fertility of these males.