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.
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
Uptake of fertility preservation procedures (eg. egg and embryo freezing) prior to cancer treatment is increasing and women will return to use these to try to conceive. Radiation may damage the uterus and there is insufficient evidence to guide the management of those exposed to intermediate doses. The aim is to improve understanding of radiation effects on the uterus which will assist clinicians with deciding whether it can support a pregnancy, or if surrogacy should be advised.
Grant Montgomery is a genetic epidemiologist with a special interest in the causes, diagnosis, prevention and treatment of common diseases. His work is focussed primarily on endometriosis and melanoma.
This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.
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.
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
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.
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.