Epigenetic Regulation Of Male Fetal Germ Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$562,176.00
Summary
Men’s health has declined over recent decades, but the causes remain unknown. Non-genetic (epigenetic) mechanisms affecting formation and function of the male germ cells (which produce sperm) may play an important role. We will determine the role of a key epigenetic modifier on the formation and function of male germ cells, including germ cell tumours. This study will provide fundamental insights into male germ cell epigenetics, and significantly contribute to understanding men's health.
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.
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
Activin And Androgen Crosstalk During Testis Development Programs Adult Fertility
Funder
National Health and Medical Research Council
Funding Amount
$700,740.00
Summary
Fertility in men is determined by how the testis grows during fetal and juvenile life. We recently discovered that the Sertoli cells which nurse developing sperm are highly sensitive to cross-talk between testosterone and the growth factor activin during puberty. This project studies how this cross-talk is controlled to understand how altered hormone actions in boys, including exposure to harmful endocrine disrupting chemicals, reduces adult fertility.
Women are born with a limited supply of eggs and are unable to make new eggs after birth. Because of this, the number and health of eggs established within the ovary early in life influence the length of time for which a female will be fertile, her age at menopause, and the health of her offspring. This project aims to shed some light on the mechanisms that control egg supply and reproductive longevity in women by investigating the role of the cell death protein Bid within the ovary.
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.
Determing Whether Breast Stem Cells Mediate The Risk Of Developing Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$433,894.00
Summary
Whilst the outcomes for women with breast cancer have improved significantly, the incidence of breast cancer continues to increase. Research needs to focus on prevention now to try to stop the increase. Apart from age, our reproductive behaviour is the largest risk factor for breast cancer. If a woman does not bear children, or has them after 35 years of age, she is at 25-50% increased risk of breast cancer. We would like to determine whether the breast stem cells play a role in this and why.
Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and and ....Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and androgen will disrupt ExG development.Read moreRead less
Characterisation Of Cumulus Cell Molecular Mediators Of Oocyte Health
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Many women are poorly fertile because of poor egg quality due to age, disease and lifestyle. IVF can assist, but requires large doses of hormone, which can lead to significant health risks. IVM is an alternative lab technique to IVF, but has very poor success. We discovered that synthetic proteins copied from recently discovered egg proteins can be added to the egg and substantially increase IVM success. Answering why will further will aid treatment for infertile women
Exploring protease inhibitors in placental development and maturation. The placenta is essential for reproduction in many diverse species. This project aims to elucidate fundamental contributions of protease inhibitors and the proteases they target to placental development and maturation. It is expected to generate new knowledge around whether SPINTS play a fundamental role in disparate animals that independently derived a placenta, suggesting convergent genetic evolution. The project is expect ....Exploring protease inhibitors in placental development and maturation. The placenta is essential for reproduction in many diverse species. This project aims to elucidate fundamental contributions of protease inhibitors and the proteases they target to placental development and maturation. It is expected to generate new knowledge around whether SPINTS play a fundamental role in disparate animals that independently derived a placenta, suggesting convergent genetic evolution. The project is expected to result in disciplinary collaboration, produce novel models, and promote future projects in many species. The project should result in significant benefits toward advancing knowledge in reproductive biology, have economic and commercial benefits, and further enhance Australia's outstanding reputation in the field.Read moreRead less