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.
Discriminating The Roles Of Inhibin A And B In Reproductive Systems
Funder
National Health and Medical Research Council
Funding Amount
$312,576.00
Summary
Inhibin A and B are essential for the regulation of fertility based on their dual inhibitory actions on follicle stimulating hormone secretion by the pituitary and egg and sperm production in the gonads. An understanding of the mechanisms involved in inhibin A and B actions will: (1) identify novel biomarkers for the diagnosis of reproductive disorders (2) enhance the management of reproductive disorders (3) identify targets for the development of therapeutic means of modulating fertility
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.
HtrA4-induced Endothelial Dysfunction In Early-onset Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$86,073.00
Summary
Preeclampsia (PE), a life-threatening disorder of pregnancy, is characterized by a sudden increase in blood pressure in association with wide-spread endothelial dysfunction. Placenta-derived factors are believed to cause PE development. Our recent studies have identified that HtrA4, a placenta-specific serine protease may contribute to endothelial dysfunction. This study will investigate the mechanisms of HtrA4-induced endothelial dysfunction.
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.