Studies Of The Dynamic Changes In The Ovarian Follicular Basal Lamina
Funder
National Health and Medical Research Council
Funding Amount
$305,557.00
Summary
In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicle ....In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicles prior to her birth, ten of thousands in her reproductive years, and none at the menopause. Since she only ovulates about 500 in her lifetime most follicles die during the process of growing to ovulatory size. This project will examine the follicular basal lamina in order to determine its role during follicle growth and development, and when follicles die. This has important implications for the many women who have polycystic ovarian disease, whose follicles fail to grow to full size. We will be examining these ovaries directly. The research also has importance in the next phase of IVF developments.Read moreRead less
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
Effects Of Exercise And Lifestyle Management On Reproductive Function In Overweight Women With Polycystic Ovary Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$379,719.00
Summary
Polycystic ovary syndrome (PCOS) is a complex disorder present in 5-10% of women of reproductive age. It is associated with obesity, increased menstrual dysfunction and infertility and metabolic conditions such as increased serum insulin, high cholesterol, diabetes and heart disease. Lifestyle interventions aimed at reducing obesity and insulin resistance, which include dietary weight loss and physical activity, are advocated for the management of PCOS. However, while research indicates that wei ....Polycystic ovary syndrome (PCOS) is a complex disorder present in 5-10% of women of reproductive age. It is associated with obesity, increased menstrual dysfunction and infertility and metabolic conditions such as increased serum insulin, high cholesterol, diabetes and heart disease. Lifestyle interventions aimed at reducing obesity and insulin resistance, which include dietary weight loss and physical activity, are advocated for the management of PCOS. However, while research indicates that weight loss through diet improves many symptoms, there is a paucity of research evaluating the combined role of physical exercise in managing this condition. In addition, there is no research examining the optimal form of exercise that should be undertaken to achieve long-term reproductive fitness and metabolic health and consequently there is a lack of evidence-based exercise guidelines for patients with PCOS. We plan to perform a clinical study to investigate whether combining exercise with weight loss by diet in patients with PCOS provides any additional benefit for improving menstrual function, fertility and metabolic health beyond those that can be achieved using dietary restriction alone. We will also assess whether, when combined with dietary restriction, a program of physical activity incorporating both endurance and resistance exercise provides a greater benefit than the more common prescription of endurance exercise alone. This information will be used to assist in the development of guidelines for the effective management of reproductive dysfunction in patients with PCOS.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.
Fetal And Genetic Origins Of Polycystic Ovary Syndrome (PCOS) In Young Women
Funder
National Health and Medical Research Council
Funding Amount
$449,073.00
Summary
Polycystic ovary syndrome (PCOS) is a common hormonal condition which emerges at puberty and afflicts up to 10% of women. The cause of PCOS is uncertain. Symptoms include menstrual disorders, acne, obesity, and excess body hair. PCOS is of great significance for women because of the high incidence of infertility and the high risk of other serious diseases, including diabetes mellitus and endometrial cancer. PCOS is probably the most common hormonal condition among young women. The cause of PCOS ....Polycystic ovary syndrome (PCOS) is a common hormonal condition which emerges at puberty and afflicts up to 10% of women. The cause of PCOS is uncertain. Symptoms include menstrual disorders, acne, obesity, and excess body hair. PCOS is of great significance for women because of the high incidence of infertility and the high risk of other serious diseases, including diabetes mellitus and endometrial cancer. PCOS is probably the most common hormonal condition among young women. The cause of PCOS is unknown and the relationship between PCOS and the more common condition of polycystic ovaries, which often features in PCOS, is uncertain. There is evidence that genetic factors contribute to PCOS, but cannot explain certain aspects. There is also striking new evidence that abnormal growth in the womb can alter the metabolism of the baby for life, resulting in increased risks of adult disease, including diabetes and cardiovascular disease. PCOS may be another consequence of abnormal fetal growth, a suggestion that is supported by two recent studies of closely related conditions. To investigate the origins of PCOS, we propose to establish the first international study of the relationships between fetal growth, genetic factors and the presence of PCOS. In this study, we shall trace 3,260 women born in one maternity ward during 1973-75. These women, now young adults, will be invited into our study for an interview, physical examination, and a blood test. We expect 2,200 women will participate. Of this group, some 220 women with PCOS will receive further tests to investigate a range of metabolic problems. The study has the potential to illuminate the path from genetic predisposition and fetal growth, to the emergence of an important reproductive disorder with serious associated diseases in a woman s later life.Read moreRead less
The Fetal And Early Childhood Origins Of PCOS: A Prospective Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$499,116.00
Summary
The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and ac ....The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and acne. The underlying causes of PCOS are not known but are thought to arise during intrauterine (fetal) life and to be modified by aspects of childhood health, particularly overweight and obesity. Using a large and well established cohort of adolescents followed up since fetal life and throughout childhood and currently aged 13-15 years old (the Raine cohort), we will define for the first time the intrauterine and early childhood correlates of PCOS. PCOS will be diagnosed by a specialist gynacologist using current international criteria. We will then utilise extensive existing data from this cohort combined with new measurements on existing samples to determine the contribution of key factors including fetal growth restriction, low birth weight, fetal androgen exposure, rapid postnatal growth, childhood adiposity, elevated fasting glucose and insulin and age at menarche to PCOS. In this way, we will address for the first time the hypothesis that PCOS arises as a result of events during fetal life and is affected by factors during childhood. The results from these studies will improve our understanding of PCOS and eventually improve reproductive and metabolic health for a substantial population of women internationally. It is essential that these studies are conducted as soon as possible or the opportunity will be missed. Girls with persistent menstrual irregularity are likely to be commenced on hormonal treatments which will make the diagnosis of PCOS impossible.Read moreRead less
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
Insulin Resistance In Polycystic Ovary Syndrome And The Role Of Skeletal Muscle And Adipose Tissue
Funder
National Health and Medical Research Council
Funding Amount
$416,115.00
Summary
11% of women have polycystic ovarian syndrome(PCOS), characterised by insulin resistance, irregular periods and infertility. These women are prone to obesity, diabetes and potentially, heart disease. Treatments include lifestyle modifications +-- medical therapy. Lifestyle is first line, yet the best diet-exercise prescription is unclear. This study will provide insights into the cause of PCOS, will inform on the role of exercise in therapy and may identify targets for future therapies.