Female fertility and age at menopause are determined by the number and quality of eggs stored in the ovaries. For unknown reasons, two-thirds of all eggs die soon after they are made. Furthermore, a serious side effect of cancer treatment is egg death resulting in infertility and early menopause. I am unravelling the genes involved in determining whether an egg will live or die. This understanding will help us develop novel strategies to preserve fertility during aging and cancer treatment.
The Role Of Primordial Follicle Activation In Premature Ovarian Failure
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, both the quality and quantity of their eggs decline and their chances of conceiving plummets. Premature ovarian failure (POF) is a disease of infertility, diagnosed in 3% of all women, defined by the early onset of menopause before age 40. Our poor understanding of the factors that regulate female egg supply remains a major limitation in treating POF. I will study key factors responsible for controlling egg number, with practical implications for POF diagnosis and treatment.
BH3-only Proteins Are Critical For The Developmentally Programmed Death Of Oocytes: Impact On Ooctye Quality And The Fertile Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$273,537.00
Summary
The ability of women to have healthy children, and the age at which menopause occurs, are largely dependent on the number and quality of the eggs stored in their ovaries. For unknown reasons, around two-thirds of all eggs die very shortly after they are made. We are unraveling the genes involved in determining whether an egg will live or die, and are investigating the role of these genes as _quality control sentinels", responsible for ensuring that only the highest quality eggs are ovulated.
RNA Binding Protein Musashi: Role In Folliculogenesis And Oocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Women in Australian have opted for social and economic reasons to delay both marriage and childbirth. Both infertility and congenital abnormality is associated with advancing maternal age as the ovarian pool of oocytes declines in number and quality. In this project we aim to gain an understanding of the molecular mechanisms underpinning healthy oocyte development. Insights gained have the potential to alleviate miscarriage, infertility and congenital abnormalities in Australian families.
Xenobiotics - Oxidative Stress In The Mammalian Ovary
Funder
National Health and Medical Research Council
Funding Amount
$377,922.00
Summary
Synthetic chemicals called xenobiotics in the environment are capable of interfering with female fertility. Xenobiotics can trigger oocyte depletion of the ovary and infertility. Exhaustion of the oocyte population results in the menopause, loss of ovarian hormones and profoundly affects female health through increasing susceptibility to heart and bone disease. This research will characterise xenobiotic effects on the ovary and will lead to significant advances in reproductive healthcare.
The Role Of Oocyte-secreted Proteins In Primate Follicular Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$176,320.00
Summary
Mammalian eggs grow and develop in fluid filled sacks in the ovary called follicles. These structures nurture the egg for prolonged periods preparing it for ovulation and fertilisation. It has been known for some time that the quality of the follicular environment determines, in part, the developmental potential of the egg. Recent studies in mice have shown that the interaction between the egg and the follicle is in fact a two-way process, and that the egg is able to influence development of the ....Mammalian eggs grow and develop in fluid filled sacks in the ovary called follicles. These structures nurture the egg for prolonged periods preparing it for ovulation and fertilisation. It has been known for some time that the quality of the follicular environment determines, in part, the developmental potential of the egg. Recent studies in mice have shown that the interaction between the egg and the follicle is in fact a two-way process, and that the egg is able to influence development of the follicle. This project proposes to investigate these processes further in the laboratory mouse using new reagents available to us, and to extend these findings by investigating this communication pathway for the first time in a primate species. Because of the difficulty of undertaking such research using human material, we will use the marmoset monkey as a model. This exciting new development has important implications for women's health because it may help us understand why some women suffer from premature menopause or cystic ovaries, and in the longer term could help in the development of new types of contraceptives.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