Mechanisms Of DNA Damage-induced Oocyte Apoptosis And Infertility: Examination Of The Role Of BH3-only Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$495,755.00
Summary
Our ability to prevent or postpone menopause following cancer treatment, is of great importance for female fertility, health and quality of life. We will demonstrate that the death gene of the Bcl-2 family of life and death genes, Puma, is responsible for killing female germ cells after damaging treatment. When Puma is absent, sufficient high quality germ cells are able to survive damaging treatment, allowing normal fertility in mice. The quality of these rescued germ cells will be analysed in d ....Our ability to prevent or postpone menopause following cancer treatment, is of great importance for female fertility, health and quality of life. We will demonstrate that the death gene of the Bcl-2 family of life and death genes, Puma, is responsible for killing female germ cells after damaging treatment. When Puma is absent, sufficient high quality germ cells are able to survive damaging treatment, allowing normal fertility in mice. The quality of these rescued germ cells will be analysed in detail.Read moreRead less
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.
Prevalence And Genetic Mechanisms Of Neurological And Gynaecological Changes In Women Carrying Small FMR1 Expansions
Funder
National Health and Medical Research Council
Funding Amount
$411,895.00
Summary
Fragile X syndrome is one of the commonest genetic forms of mental retardation. The abnormal gene is passed from mothers to their sons or daughters, on their X chromosome. The gene abnormality is unstable, tending to worsen each time it is passed on. But if this gene abnormality is passed from fathers to their daughters, it does not worsen. Therefore, grandfathers of the affected children on their mother's side, as well as the mothers, may carry a mildly abnormal gene (a premutation), insufficie ....Fragile X syndrome is one of the commonest genetic forms of mental retardation. The abnormal gene is passed from mothers to their sons or daughters, on their X chromosome. The gene abnormality is unstable, tending to worsen each time it is passed on. But if this gene abnormality is passed from fathers to their daughters, it does not worsen. Therefore, grandfathers of the affected children on their mother's side, as well as the mothers, may carry a mildly abnormal gene (a premutation), insufficient to cause mental retardation. However, it has recently been discovered that these grandfathers may develop a syndrome (FXTAS) of tremor, incoordination, slowness of movements and mild dementia in their later years. Women were thought to be protected, as they carry TWO X chromosomes, one of which is normal even if the other has a premutation. But very recent reports suggest that they may also develop the FXTAS syndrome, as well as early menopause. This study aims to see how common and severe these abnormalities are in women who carry the premutation, using clinical, MRI and electronic measurements, and to relate the abnormalities to the severity of the gene malfunction and familial predisposition.Read moreRead less
Leveraging Women’s Health Data Resources To Reduce Chronic Disease Risk And Extend Healthspan
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Chronic diseases, such as osteoporosis and asthma, pose serious risks for Australian women. Reproductive health is central to women’s use of health services across life and is linked with the risk of chronic diseases. This research will build on two decades of linked data in Australia’s leading study of women’s health. It aims to guide development of women’s use of reproductive and maternal health services as an opportunity to prevent chronic diseases and improve long-term health.
Physiological Consequences Of The Loss Of Inhibin Activity
Funder
National Health and Medical Research Council
Funding Amount
$613,035.00
Summary
Inhibin A and B are essential factors in mammalian reproduction, negatively regulating pituitary production of follicle stimulating hormone (FSH). Interestingly, declines in inhibin levels at menopause correlate with a rapid decrease in bone and muscle mass. We propose that inhibin A and B have important physiological roles in the stimulation of bone and muscle growth, and that inhibins could be utilised to treat postmenopausal complications, including osteoporosis and sarcopenia.
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 failure of an embryo to implant is a major cause of infertility. While IVF is an important intervention, still three quarters of embryos do not implant. We have identified new factors that we believe are critically important in embryo attachment to the womb. We will now prove whether these factors are critical and therefore provide the evidence required to begin to develop novel treatment options for infertility.
Female Reproductive Health Preservation By Nicotinamide Adenine Dinucleotide (NAD+) And Sirtuin2 (SIRT2)
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Cancer treatment can be severely toxic to women’s eggs. Increasing numbers of women who survive cancer therefore become infertile and prematurely deprived of hormonal support whilst still in their reproductive years. This project will use state-of-the-art techniques to interrogate newly uncovered pathways that can protect eggs from treatment-induced injury thereby greatly improving the quality of life for female cancer survivors.
Genetic Variations And Dopaminergic Contributions To Prefrontal Cognitive Systems In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$169,904.00
Summary
Depression and cognitive change associated with menopause frequently occur, but are poorly understood. This research will allow for a greater understanding of the nature of the relationship between menopause, depression and cognitive impairment. The exploration of the efficacy of hormonal and antidepressant treatment on both mood and cognition will contribute to a better understanding to allow for improved treatment options.
Macrophages In Developmental Programming Of Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$532,386.00
Summary
Programming of reproductive health in women begins long before sexual maturity. Development during childhood, puberty and adulthood produces a fully functional reproductive system capable of conceiving, gestating and nurturing a child. This project will investigate the role of immune cells known as macrophages in the reproductive system, and investigate how their disruption might influence developmental programming and have lifetime consequences for the reproductive health of the individual.