This study is aiming to develop an unique mouse model in which to study the question whether testosterone plays an essential role in female reproductive and general health. It will develop a genetic mouse model for a biological state of complete resistance to the effects of androgens. Such mice and humans are well known among genetic males but this cannot occur naturally among genetic female mammals. By creating such a mouse line, this project will be able to test for the first time indetail whe ....This study is aiming to develop an unique mouse model in which to study the question whether testosterone plays an essential role in female reproductive and general health. It will develop a genetic mouse model for a biological state of complete resistance to the effects of androgens. Such mice and humans are well known among genetic males but this cannot occur naturally among genetic female mammals. By creating such a mouse line, this project will be able to test for the first time indetail whether testosterone has an impotant role in the development and function of the ovary and of other female tissues such as bone, muscle and the brain.Read moreRead less
Androgen Receptor Mechanims In Female Reproductive Physiology
Funder
National Health and Medical Research Council
Funding Amount
$539,773.00
Summary
Infertility occurs in one in six Australian couples with 50% attributable to females, thus, enhancing our understanding of ovarian and uterine function is of great importance. This project tests the proposal that androgens (steroid hormones) play a major role in regulating female reproductive physiology through their interaction with the androgen receptor. We have developed novel mouse models which we will use to determine the roles of androgens in regulating female reproductive function.
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.
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.
Androgen Receptor Activity In Normal And Abnormal Human Ovarian Function
Funder
National Health and Medical Research Council
Funding Amount
$416,696.00
Summary
Androgens are hormones normally associated with men, but women also produce androgens and they are essential for normal female health and reproduction. Imbalances in female androgen activity could account for approximately 50% of female infertility, but exactly how androgens behave in women is not well understood. Making too much androgen is the most common hormonal problem experienced by women in their reproductive years, and it affects the ovary in a way that can cause infertility. Women with ....Androgens are hormones normally associated with men, but women also produce androgens and they are essential for normal female health and reproduction. Imbalances in female androgen activity could account for approximately 50% of female infertility, but exactly how androgens behave in women is not well understood. Making too much androgen is the most common hormonal problem experienced by women in their reproductive years, and it affects the ovary in a way that can cause infertility. Women with this problem have polycystic ovary syndrome (PCOS). Gaining weight increases the chance of having problems with fertility and increases the risk of diabetes and heart problems in women with PCOS. The cause of PCOS is unknown, but it can occur in families, which indicates that some genetic factor is involved. On the other hand, the concept that some women do not produce enough androgen is only beginning to emerge and remains a controversial topic among medical experts. Part of the problem with this notion is that normal female androgen levels are very difficult to measure accurately, so no one can say for certain how much is too little. A recent scientific study in female mice indicates that poor androgen action causes infertility early in life because the ovary is ageing too quickly. A similar thing could possibly occur in women, but this has never been scientifically explored. However, we have some early evidence that shows abnormally low androgen levels in infertile women with signs of early aging in the ovary. Our study aims to understand the role that androgens play in normal and abnormal ovarian function. A large part of this study involves investigation of the androgen receptor, a molecule that controls what androgens can do inside body organs. We think that abnormal activity of this receptor will be involved in ovarian diseases that cause infertility in women. This understanding may lead to new means of diagnosing and treating infertility in women.Read moreRead less
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
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