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.
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
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.
Cysteine-rich Secretory Protein Regulation Of Ion Channels In Male Fertility And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$474,309.00
Summary
Diagnosis of the precise causes of male infertility and the development of male contraceptives requires improved understanding of sperm function. The Cysteine-Rich Secretory Proteins (CRISPs) are produced in the male reproductive tract where they regulate sperm function. Our project will demonstrate the essential requirement for CRISPs in sperm function and investigate their role in other tissues of the reproductive tract, including the prostate where they may be involved in prostate cancer.
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.
Cumulus Cell Invasive Migration: Clearing A Path For The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$409,684.00
Summary
Ovulation is the process by which the egg is released from a female�s ovary, but it is not known how this process is controlled. We found that cells surrounding the egg are motile and similar to cancer cells; thus we hypothesize that this enables the egg to _invade� its way out of the ovary. We will test this idea in mice and determine whether similar processes are happening in women. The results will provide new information about how to stop ovulation and aid women who experience infertility.
The Mechanism Of Spermatid Differentiation - A Link To Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$506,425.00
Summary
To discover novel regulators of male fertility, we have screened libraries of mutant mice generated by a chemical mutagen. This project aims to define the function of the mutated gene identified in a male-specific infertile mutant mouse line. The mutated gene has been proposed to play a role in regulating cell death and suppress lung tumour formation. Our data may reveal novel options for male infertility treatment and for the development of male contraception and lung cancer biomarkers.
Why We Have Two Estrogen Receptors: The Role Of ERbeta In Folliculogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$576,053.00
Summary
The female hormone estrogen acts via receptors ERalpha and ERbeta. Little is known about the genes and proteins regulated by ERbeta. Ovarian granulosa cells and granulosa cell tumours express ERbeta. By studying the biology of normal and malignant granulosa cells we hope to understand the role that ERbeta plays in granulosa cells. These studies will identify areas for the development of new therapeutics or treatment strategies for a range of female-specific conditions including ovarian cancer.
Follicle-stimulating hormone (FSH) is vital for egg development, female fertility and health, and is widely used in assisted reproduction technology. But high levels of FSH are associated with premature infertility and menopause, and may lead to diseases like ovarian cancer. Understanding the biological pathways activated by elevated FSH may lead to new treatments for infertility and ovarian diseases (eg. cancer), as well as advancing new strategies for contraception.