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.
Molecular Characterization Of Unique Recognition Sites On The Surface Of Human Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do ....Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do we understand which particular aspect of sperm biochemistry is defective. As a consequence we have not been able to develop sensitive biochemical diagnostic tests for the infertile male nor do we have any rational methods of treatment that address the cause of this condition. Similarly no new methods of male fertility regulation have been introduced since vasectomy despite the major advances that have been made in the field of female contraception over the same period of time. Clearly if we are to develop sensitive methods for the diagnosis of defective sperm function, introduce protocols for the treatment and prevention of male infertility and discover novel approaches to male contraception, we must first understand the cellular mechanisms that enable these highly specialized cells to perform their unique function. In this study we shall focus on one of the most important attributes of sperm function the capacity of these cells to recognize the egg. Once the biochemical basis of this fundamental recognition process is understood, it should pave the way for the development of clinical applications that target this signaling system with implications for a range of disciplines including reproductive toxicology, occupational medicine, family planning, infertility and biotechnology.Read moreRead less
RNA Binding Protein Musashi: Role In Folliculogenesis And Oocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Women in Australian have opted for social and economic reasons to delay both marriage and childbirth. Both infertility and congenital abnormality is associated with advancing maternal age as the ovarian pool of oocytes declines in number and quality. In this project we aim to gain an understanding of the molecular mechanisms underpinning healthy oocyte development. Insights gained have the potential to alleviate miscarriage, infertility and congenital abnormalities in Australian families.
Biomarkers For The Diagnosis And Prognostic Analysis Of Male Infertility
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Male infertility is a common condition, affecting 1 in 15 men. Although a standard semen analysis is often performed to test whether a man is infertile, it is far from definitive. We have developed a new approach, by looking at proteins that are commonly missing from infertile sperm cells. From this analysis, we can definitively diagnose male infertility and are beginning to understand why men are becoming infertile.
The Role Of Dynamin In Spermatogenesis, Sperm Maturation And Sperm-oocyte Interactions
Funder
National Health and Medical Research Council
Funding Amount
$551,950.00
Summary
Male infertility is an extremely common condition affecting 1 in 20 Australian men. One of the major reasons for this pathology is that the spermatozoa have lost their ability to interact with the egg and penetrate its outer vestments. In this project we shall investigate the role of dynamin in the regulation of these events. This research will provide new and powerful insights into the causes of male infertility, with practical implications for diagnosis and treatment of this condition.
Investigation Of The Mechanisms Underpinning HSPA2 Dysfunction In The Spermatozoa Of Infertile Patients
Funder
National Health and Medical Research Council
Funding Amount
$481,563.00
Summary
Male infertility is an extremely common condition, that is frequently associated with the production of sperm that have lost their ability to recognize the egg. We have shown that this defect is frequently associated with a deficiency in a specific protein (HSPA2). By determining the mechanisms underpinning the loss of HSPA2, this project will provide powerful insights into the causes of male infertility, with practical implications for prevention, diagnosis and treatment of this condition.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
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
Leucine-rich Guanylate Kinase Is A Regulator Of Sperm Tail Development And Motile Cilia Function
Funder
National Health and Medical Research Council
Funding Amount
$540,191.00
Summary
In this grant we will define the function of an uncharacterized protein, LRGUK, in fertility and hydrocephalus (water on the brain). LRGUK has a critical role in sperm development. We will define the cell biology and biochemistry of LRGUK function, we will assess the incidence of LRGUK mutations in human fertility and explore LRGUK function in the brain. Data obtained will have relevance to the 1 in 20 young men who suffer from infertility and the 3 in 1000 children who develop hydrocephalus.