Hypospadias is one of the most common developmental defects in humans, yet over two thirds of the cases cannot be explained. Our recent studies using marsupials show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. This study will provide novel data on the interactions of the genes and hormones that will inform our understanding of this common developmental defect of male development
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.
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.
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.
The Role Of Placental Transcription Factors In The Pathogenesis Of Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$601,582.00
Summary
We must understand the role of growth control genes in the growth of the human placenta. The reason is that in several significant placental disorders, placental formation is abnormal and prevents the placenta from functioning efficiently. This in turn, impacts on the growth of the developning fetus. A variety of established and innovative methods described in this project will determine the functions of the placental growth control genes and may lead to novel therapeutic targets.
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
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
Isolation And Function Of Human Oogenesis Genes Regulating Meiosis, Recruitment, Growth And Maturation Of The Oocyte.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes ....Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes that form the follicles containing the developing germ cells and the matured oocytes needed for IVF. The cohort of oocytes that can be harvested from any patient depends on unknown recruitment processes initiating development of a subset of the quiescent germ cells and happens in an unregulated and spontaneous manner. The present project will identify the known and unknown genes involved in recruitment of oocytes from the basal primordial population. These genes will become candidates for aiding infertile women, improving their response to fertility drugs, the development of novel contraceptive methods and potentially increasing the reproductive life span of women. Knowledge of the genes expressed in oocytes matured in vivo and in vitro will have an important bearing on the long-term opportunity to use fertility drugs in vitro instead of administration to patients for IVF. This would dramatically reduce the cost of IVF and the side-effects of hyperstimulation of ovaries of patients and the associated sequelae. The research project is a discovery program leading to the identification of the genes that govern oogenesis in the human. It is only recently that techniques have been developed to sufficient sensitivity to detect the small quantities of RNA proceeded by active genes in the individual germ cells and oocytes.Read moreRead less
The Long-term Consequences Of Assisted Reproduction On The Growth, Metabolic, Respiratory, Psychological, Immunological And Reproductive Development Of The Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$1,552,096.00
Summary
1 in 25 children are born from IVF treatment - incredibly- to our shame; no data exists as to the long-term health of these children. Presented is a unique opportunity, which would be exceedingly difficult to replicate elsewhere in the world, to determine the long-term consequences of IVF upon the development of the offspring, by comparing their growth, metabolic, respiratory, psychological, immunological and reproductive development to a representative sample of WA children- the Raine cohort.