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
Gastrointestinal Function And Appetite In Obesity - Acute And Longer-term Effects Of Changes In Energy Intake
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
The prevalence of obesity is assuming epidemic proportions. While weight loss diets help people to lose weight, body weight stabilises over time despite continued dieting. Our research proposal represents a novel initiative with the aim to understand the adaptations in gastrointestinal mechanisms in response to acute and longer-term dietary restriction that compromise weight loss. Ultimately our research will help to develop weight loss strategies that are successful in the long-term.
Functional Genomic Analysis Of The Role Of P53 In Early Embryo Death After Assisted Reproductive Technologies (ART).
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only ....Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only modest increments in embryo survival in recent years. The low cahnce of individual embryos resulting in a baby means that: (1) generally several treatment cycles are required; (2) superovulation is used to maximise the number of embryos produced giving an accumulation of unwanted cryopreserved embryos; (3) more than one embryo is generally transferred resulting in a significant incidence of multiple pregancies. The high mortality of the early embryo seems to be a general feature of IVF but its causes and effectors are not known. It has recently been established that it largely occurs due to a form of cell 'suicide' known as apoptosis. This form of cell death has important normal functions: its activation allows for cells that are no longer required to be removed, allowing the remodelling of tissues and it also serves to remove cells that are irreversibly damaged. p53 is a protein that has the ability to 'sense' cell stress and damage and to direct the cell to undergo apoptosis if the stress is severe. This project will examine if ART cause increased expression of p53 and whether this elevation of p53 causes embryonic cell death. We will examine the factirs that control p53 expression in the embryo. using mice with mutations that stop the function of p53 and several of its regulatory proteins. Experiments will determine the susceptibility of embryos possessing these mutations and will therefore allow us to define the proteins causing apoptosis after ART.Read moreRead less