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.
Focus On The Uterus: Basic And Translational Research Strategies To Address Key Issues In Women’s Health. Fertility, Infertility, Endometrial And Pregnancy Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$1,085,790.00
Summary
My work focuses on the endometrium, the lining of the uterus, into which the embryo implants to establish pregnancy. When the endometrium does not function correctly, the woman is usually infertile. Other disorders of the endometrium include endometriosis, menstrual bleeding problems and cancer. My studies have defined the molecular basis for much endometrial dysfunction. I am now developing non-invasive tests for these problems and rationales for new treatments.
Cumulus Cell Invasive Migration: Clearing A Path For The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$409,684.00
Summary
Ovulation is the process by which the egg is released from a female�s ovary, but it is not known how this process is controlled. We found that cells surrounding the egg are motile and similar to cancer cells; thus we hypothesize that this enables the egg to _invade� its way out of the ovary. We will test this idea in mice and determine whether similar processes are happening in women. The results will provide new information about how to stop ovulation and aid women who experience infertility.
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.
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.
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.
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.
Gonadotropin Inhibitory Hormone As A Major Regulator Of Reproduction In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$623,378.00
Summary
Reproduction is controlled by the brain and it has been well established that gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. GnRH stimulates the pituitary gland to produce and secrete hormones that, in turn, stimulate the ovaries and testes. It is becoming clear that the brain also produces an inhibitory factor and this project aims to establish that it (gonadotropin inhibitory hormone; GnIH) is functional in mammals.
Cohesin: Role In Germ Cell Chromosomal Segregation
Funder
National Health and Medical Research Council
Funding Amount
$435,526.00
Summary
At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related gen ....At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related genes, called Rec8 and Rad21, which we recently discovered in humans and mice. Due to that these genes are essential for chromosome separation in other species and they exists in species as diverse as yeast and humans, they may be responsible for accurate separation of chromosomes in germ cells in mammals. In this proposal, we will determine the role(s) of these molecules in controlling proper chromosome segregation by loss-of-function studies in genetically engineered mice lacking Rec8 and Rad21 genes. By analyzing the chromosomal abnormalities of the cells from these animals, we will gain critical information about the nature of chromosome partitioning disorders in humans.Read moreRead less
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