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
The Role Of FSH And FF-MAS In The Induction Of Meiotic Resumption In The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order ....About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order to produce many eggs, thereby increasing the success rate per treatment cycle. But stimulation of ovarian function involves a number of drawbacks including cost of fertility drugs, continued monitoring, discomfort and risk of complications (eg. ovarian hyperstimulation syndrome). It is evident that novel methods for the production of mature eggs in vitro in the absence of ovarian stimulation would mark a breakthrough, making assisted reproduction a more friendly discipline. In general, all IVF patients would benefit from in vitro maturation techniques. In particular, in selected patients (eg. those suffering from polycystic ovary syndrome) the advantages of this method might prove to be invaluable, by achieving production of fully viable eggs under controlled conditions, as opposed to in vivo where oocytes generally fail to acquire full competence, having been subjected to an unfavourable hormonal environment. Unfortunately, attempts to treat IVF patients using eggs matured in vitro has been disappointing so far, with only occasional pregnancies reported over the last decade. Clearly, this is due to lack of knowledge of the fundamental events occurring during egg maturation, as well as the paucity of biological material available for experimentation. So, to make in vitro maturation of eggs a successful fertility treatment we undoubtedly need to achieve a more profound insight into the function of the egg, the first step being to focus our attention upon experimental models.Read moreRead less