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.
Cysteine Rich Secretory Proteins (Crisp) Are Ion Channel Regulators With Essential Roles In Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
Male infertility affects 1 in 20 Australian men and for the majority of other men, contraception is an issue at some point in their lives. Despite this, relatively little is known about the processes of sperm production and fertilization. As such, there is an urgent need for futher research if we are to hope to develop diagnostics, targeted therapeutics and to take advantage of the growing awareness by pharmaceutical companies of the market for male gamete based contraceptives. The cysteine rich ....Male infertility affects 1 in 20 Australian men and for the majority of other men, contraception is an issue at some point in their lives. Despite this, relatively little is known about the processes of sperm production and fertilization. As such, there is an urgent need for futher research if we are to hope to develop diagnostics, targeted therapeutics and to take advantage of the growing awareness by pharmaceutical companies of the market for male gamete based contraceptives. The cysteine rich secretory proteins (Crisps) are a group of proteins which show a remarkable bias to the male reproductive tract. All four are incorporated into sperm. Recently published data from us indicates that they have the ability to regulated calcium flow in sperm and as such sperm activity. The aim of the current proposal is to explore the biological relevance of one domain of Crisp proteins using animal models, in vitro sperm tests and through an analysis of ion flux and phosphorylation status under conditions of altered Crisp-1 and -2 content. The data generated from this project will make a significant contribution to the development of novel male gamete based contraceptives for use by either men or women. In addition, through the attainment of a greater understanding of sperm development and function, we will be able to more precisely define types of infertility, thus allowing for the development of more targeted therapies. The development of Crisp agonists or antagonists may also be of value in the treatment of other cilia disorders including primary cilia dykinesia and cystic fibrosis.Read moreRead less
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.
Approximately 1 in 25 men in the western world are infertile, and while environmental and genetic factors are recognized to contribute to disease, there is currently a poor understanding of the basic mechanisms regulating male fertility. Our long term goal is to identify and study key molecules involved in sperm production. Understanding the role of these molecules will provide insight into the causes of male infertility. Ultimately, these studies will assist to develop new treatments for male r ....Approximately 1 in 25 men in the western world are infertile, and while environmental and genetic factors are recognized to contribute to disease, there is currently a poor understanding of the basic mechanisms regulating male fertility. Our long term goal is to identify and study key molecules involved in sperm production. Understanding the role of these molecules will provide insight into the causes of male infertility. Ultimately, these studies will assist to develop new treatments for male reproductive disorders. Conversely, there is a huge need for additional male based contraceptives. Increased understanding of male fertility and identification of proteins exclusively involved in sperm production provides the opportunity to develop new contraceptive treatments.Read moreRead less
Redox Cycling Of Quinones By Human Spermatozoa: A Potential Strategy For The Dual Regulation Of Fertility And STDs
Funder
National Health and Medical Research Council
Funding Amount
$314,625.00
Summary
The purpose of this research project is to develop a novel form of contraception that could meet the dual objectives of fertility regulation and prevention of sexually transmitted disease (STD). A particularly novel feature of this proposed spermicide-microbicide is that it has to be activated by spermatozoa i.e the formulation comprises a pro-spermicide that only generates the active principle on contact with sperm. This aspect of the method sets it apart from all other forms of topical contrac ....The purpose of this research project is to develop a novel form of contraception that could meet the dual objectives of fertility regulation and prevention of sexually transmitted disease (STD). A particularly novel feature of this proposed spermicide-microbicide is that it has to be activated by spermatozoa i.e the formulation comprises a pro-spermicide that only generates the active principle on contact with sperm. This aspect of the method sets it apart from all other forms of topical contraception because unlike barrier methods and vaginal creams or foams, its use will not be coitus related. Ultimately it is envisaged that the product could be incorporated into a soft pliable vaginal sponge and left in situ until such time as it becomes activated following intercourse. Such a method should be particularly acceptable to young women who are vulnerable to both STDs and unwanted pregnancy as indicated by (a) the relatively high rates of STDs in adolescent girls, particularly in the indigenous community, and (b) the fact that 50% of all recorded pregnancies to Australian women under 19 years of age end in abortion. The method exploits the susceptibility of human spermatozoa and pathogenic organisms responsible for STDs to oxidative stress and, in effect, mimics a naturally occurring cause of male infertility. If successful, this project would produce a female centred method of contraception and STD prevention that would revolutionize reproductive health care for young women worldwide, as well as generating intellectual property of considerable potential value to the nation.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.
Improving The Quality Of Oncofertility Care In Children, Adolescents And Young Adults With Cancer: Implementation Of A Novel Fertility Preservation Decisional Support Tool To Translate Evidence Into Best Practice
Funder
National Health and Medical Research Council
Funding Amount
$177,197.00
Summary
International guidelines recommend the discussion about the impact of cancer treatment on fertility. Lack of information about fertility is cited by parents as the most unmet information need.This proposal, aims to a. Develop decisional support tools for clinicians that will enhance the quality of oncofertility discussions; b. develop a Decision Aid for families making oncofertility decisions; c. Publish summaries of evidence that can contribute to national guidelines.