I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
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.
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.
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.
Orexins As Neuroendocrine Integrators Between Nutrition And Reproduction Control Systems
Funder
National Health and Medical Research Council
Funding Amount
$332,036.00
Summary
Studies on humans and a range of animal species have shown that the effects of nutrition on reproduction are mediated at least partly by changes in the secretion of gonadotrophin releasing hormone (GnRH) and thus gonadotrophins. A number of metabolic signals must also be involved but those tested to date (glucose, insulin, leptin) do not seem to play major roles. Two exciting new candidates are orexin-A and orexin-B, a recently discovered pair of peptides that stimulate feeding behaviour. They a ....Studies on humans and a range of animal species have shown that the effects of nutrition on reproduction are mediated at least partly by changes in the secretion of gonadotrophin releasing hormone (GnRH) and thus gonadotrophins. A number of metabolic signals must also be involved but those tested to date (glucose, insulin, leptin) do not seem to play major roles. Two exciting new candidates are orexin-A and orexin-B, a recently discovered pair of peptides that stimulate feeding behaviour. They are synthesized in the brain and, in rodents, they either stimulate or inhibit gonadotrophin secretion, depending on the presence of sex steroids. In this project, we will investigate the roles of the orexins as integrators of signals about gonadal activity, nutrition and body condition, all of which affect the activity of the reproductive control centres in the brain. We will use the mature male sheep because it shows clear and repeatable reproductive responses to changes in nutrition. We will locate the orexin-producing cells and the cells that respond to the orexins, and show how orexin production is affected by diet. We will also study the ways in which the orexins affect, and are affected by, the hormone systems that control reproduction and metabolism. Finally, we will try to find out why there are two orexins by looking at how their actions differ. Ultimately, the orexin system might explain the brain processes that are behind many of the reproductive problems that are associated with metabolic disorders, such as appetite loss, excessive exercise, undernutrition, polycystic ovarian syndrome, and insulin-dependent diabetes.Read moreRead less
Targeting The Gonadotropin-releasing Signal Transduction Cascade Novel Approaches To Regulating Reproduction And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$438,625.00
Summary
We know that nutrition and reproduction are closely linked e.g. undernutrition leads to infertility, menopause to weight gain, but we do not know precisely the mechanisms whereby these events occur. The brain hormone gonadotropin-releasing hormone (GnRH), which stimulates the reproductive pathways and a recently discovered family of hormones (orexins) which stimulate feeding both act through the same type of recognition site i.e. G-protein coupled receptors (GPCRs) which are distributed in close ....We know that nutrition and reproduction are closely linked e.g. undernutrition leads to infertility, menopause to weight gain, but we do not know precisely the mechanisms whereby these events occur. The brain hormone gonadotropin-releasing hormone (GnRH), which stimulates the reproductive pathways and a recently discovered family of hormones (orexins) which stimulate feeding both act through the same type of recognition site i.e. G-protein coupled receptors (GPCRs) which are distributed in close proximity within the brain. Identifying how these two pathways interact has enormous potential for the treatment of disorders of weight and-or reproduction since the GPCR structure and the route by which it signals lends itself to therapeutic intervention.Read moreRead less
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.
Effects Of Leptin On Follicle Growth And Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$196,470.00
Summary
Leptin is a recently discovered hormone which is very important in controlling body weight. Extremely obese, or extremely underweight women, find it difficult to become pregnant, and leptin is probably the connection between weight and fertility. This may be a particularly important factor in polycystic ovary syndrome (PCOS), a distressing condition which affects 5% of women and causes both obesity and infertility. Exciting new research suggests that leptin also affects the immune system, and pr ....Leptin is a recently discovered hormone which is very important in controlling body weight. Extremely obese, or extremely underweight women, find it difficult to become pregnant, and leptin is probably the connection between weight and fertility. This may be a particularly important factor in polycystic ovary syndrome (PCOS), a distressing condition which affects 5% of women and causes both obesity and infertility. Exciting new research suggests that leptin also affects the immune system, and previous NH and MRC funding has enabled us to demonstrate that the immune system plays a crucial role in maintaining normal ovarian function. The nutritional status of the body, the immune system and the reproductive system all interact, and leptin appears to be the connecting link between these three major systems. We propose that leptin plays a major role in the ovary, and wish to determine how leptin mediates the effects of bodyweight and the immune system on ovarian function. Laboratory rats will be treated with leptin, their food intake and weight recorded, and a few weeks later the rats will have their ovaries removed. We will find out whether ovaries respond to leptin, or whether the ovarian response changes according to the menstrual cycle: perhaps leptin is very important just before ovulation, but it does not affect menstruation? Do any ovarian cells make leptin? Will leptin stimulate ovaries to produce more oestrogen or progesterone, or ovulate more eggs? We will also identify immune system cells in the ovary, and note whether leptin affects them. We will be able to relate all this data to weight and diet. Increased understanding of leptins' effect on the ovary has the potential to lead to new, improved treatments for PCOS or for unexplained cases of infertility. It is also possible that in the future a weight-loss regime might be developed which takes a womans monthly cycle into account, therefore making weight-loss more efficient and attainable.Read moreRead less