The Function Of Gametogenenin In Male Fertility And Embryogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,579.00
Summary
We have identified gametogenetin as novel protein involved in sperm production and in the very earliest stages of embryo survival. It is found within the sperm tail where it binds to cysteine-rich secretory protein 2. The aim of this project is to further refine the biochemistry of GGN using a combination of binding studies, expression analyses and the characterization of two unique mouse models. This project has direct relevance to the causes of human infertility and contraceptive development.
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.
Kisspeptin And Its Receptor Mastermind Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Reproduction is controlled by the brain and gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. Finding critical regulators of GnRH has remained the most important goal for reproductive endocrinologists for over 30 years. The brain peptide hormone called kisspeptin and its receptor Kiss1R appear vital in the control of reproduction. This project will detail the role kisspeptin and Kiss1R play in controlling hormones from the brain that govern puberty and reproduction.
The Identification Of Male Meiosis Genes Using A New Mouse Line And Human Genome Scans For Gene Copy Number Variations
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Infertility affects 1 in 25 Australian men and meiosis is a key process in male fertility, yet we know very little about the mechanisms that control it. We will use a new point mutant mouse model of meisois failure to identify a novel regulator of male fertility. Further, we hypothesize that changes in gene copy number will lead to meiosis arrest and infertility in some men. Such variations will be assessed through a whole genome scan of a unique set of infertile men.
Reproduction is controlled by the brain through the hormone gonadotropin releasing hormone (GnRH). Leptin from fat acts on the brain to 'inform' GnRH cells of metabolic state; low levels signal lack of energy stores and suppress reproduction. Leptin treatment of lean individuals restores reproductive function, but the mechanism is not clear. Our data implicate the melanocortins as a means of transmitting information on metabolic state to GnRH cells and the project investigates this pathway.
Identification Of Novel Common Genetic Risk Factors For Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$593,783.00
Summary
Multiple genetic factors underlie susceptibility to endometriosis—a common gynaecological disease associated with severe pelvic pain and sub-fertility. Through the identification of novel genetic risk factors and pathway-based analyses, this project will increase our understanding of the underlying genetic architecture and complex molecular pathways of endometriosis and lead to the development of diagnostic tests and rational treatment strategies.
A New Model Of Asthenospermia And A Candidate Gene For Multiple Ciliopathies
Funder
National Health and Medical Research Council
Funding Amount
$629,039.00
Summary
Though the analysis of a unique mouse strain (Mot1) we have identified a previously unknown cause of male infertility and lung disease. We hypothesis that the Mot1 line is a model of human primary cilia dyskinesia and that the Mot1 protein is involved in cilia function. Within this project we will define the consequences of a loss of Mot1 protein function, we will define its binding partners and we will screen for mutations in the corresponding human gene.
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
Reproductive health critically impacts a woman’s wellbeing, irrespective of her choice to have children. The ovary and its hormones govern physiological events regulating health at puberty, across the menstrual cycle, during the establishment and maintenance of pregnancy, and in parturition, lactation and menopause. The major health burdens concerning ovaries that we are studying include polycystic ovarian syndrome and assisted reproductive technologies used to treat infertility.