Why We Have Two Estrogen Receptors: The Role Of ERbeta In Folliculogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$576,053.00
Summary
The female hormone estrogen acts via receptors ERalpha and ERbeta. Little is known about the genes and proteins regulated by ERbeta. Ovarian granulosa cells and granulosa cell tumours express ERbeta. By studying the biology of normal and malignant granulosa cells we hope to understand the role that ERbeta plays in granulosa cells. These studies will identify areas for the development of new therapeutics or treatment strategies for a range of female-specific conditions including ovarian cancer.
Follicle-stimulating hormone (FSH) is vital for egg development, female fertility and health, and is widely used in assisted reproduction technology. But high levels of FSH are associated with premature infertility and menopause, and may lead to diseases like ovarian cancer. Understanding the biological pathways activated by elevated FSH may lead to new treatments for infertility and ovarian diseases (eg. cancer), as well as advancing new strategies for contraception.
Cognitive Effects Of Adding Ovarian Function Suppression To Adjuvant Hormonal Therapy In Premenopausal Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$301,431.00
Summary
There is mounting evidence that potentially curative treatment for breast cancer might, in some women, have an adverse effect on their subsequent cognitive function i.e. their memory and ability to think clearly. Thus it is important that when new treatments are being tested, the testing includes collecting information on the effect of the new treatment on a woman's cognitive function. There is currently an ongoing large international study examining whether suppressing ovarian function (and thu ....There is mounting evidence that potentially curative treatment for breast cancer might, in some women, have an adverse effect on their subsequent cognitive function i.e. their memory and ability to think clearly. Thus it is important that when new treatments are being tested, the testing includes collecting information on the effect of the new treatment on a woman's cognitive function. There is currently an ongoing large international study examining whether suppressing ovarian function (and thus decreasing oestrogen levels) in women having treatment for breast cancer will improve their outcomes. However,it is known that oestrogen is important for normal cognitive functioning in premenopausal women so there is some concern that dropping the oestrogen levels in this way might cause impairment in cognitive function. In this sub-study we will compare the cognitive function of women having ovarian function suppression with those who do not, to determine if there are any differences. We will also examine how this might affect quality of life.Read moreRead less
Studies Of The Paracrine Role Of Inhibin A/activin A In Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enor ....This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enormous difference to women s health in the following areas: contraception, the possibility of development of new methods of contraception that block egg release without affecting the normal ovarian cycle endocrinology; fertility treatment, better methods of obtaining mature oocytes without subjecting women to high dose gonadotrophin treatment and the accompanying sequelae; improving knowledge of the factors that promote satisfactory oocyte maturation and embryo development so that with improved implantation rates, fewer embryos need be replaced to achieve a pregnancy.Read moreRead less
Positional Candidate Targets For Multiple Ovulation Genes
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
The frequency of non-identical twins is associated with fertility in individuals and populations, although we know little about mechanisms for twinning or effects on fertility. The likelihood for giving birth to non-identical twins is influenced by genetic factors. The probability of a subsequent twin pregnancy is increased fourfold in mothers of twins and roughly doubled for women whose mother or sister has had non-identical twins. Understanding why some women are more likely to have twins will ....The frequency of non-identical twins is associated with fertility in individuals and populations, although we know little about mechanisms for twinning or effects on fertility. The likelihood for giving birth to non-identical twins is influenced by genetic factors. The probability of a subsequent twin pregnancy is increased fourfold in mothers of twins and roughly doubled for women whose mother or sister has had non-identical twins. Understanding why some women are more likely to have twins will help us find key pathways that control normal ovarian function and important factors that influence success in assisted reproduction. The aim of this project is to search for these genes in families with two sisters who have given birth to non-identical twins. Previous studies have identified one strong target region and two possible regions containing genes for increased twinning. We now have additional families and will examine each region in more detail. We will also look for genes within each region that could be responsible for variation in twin frequency.Read moreRead less
Defects of the internal and external genitalia are among the most common birth defects in babies (1 in 4,000 births) yet the aetiology in many cases is unclear. We will compare and contrast the mouse with a unique animal model the tammar wallaby to investigate the control of ovarian differentiation during early fetal and postnatal life. The gonad is unusual in that two completely different organs arise from the same precursor tissues, so that errors in development lead to intersexual phenotypes. ....Defects of the internal and external genitalia are among the most common birth defects in babies (1 in 4,000 births) yet the aetiology in many cases is unclear. We will compare and contrast the mouse with a unique animal model the tammar wallaby to investigate the control of ovarian differentiation during early fetal and postnatal life. The gonad is unusual in that two completely different organs arise from the same precursor tissues, so that errors in development lead to intersexual phenotypes. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutations. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. We will use comparative analysis and an inducible sex reversal system to understand the way gene expression and hence tissue differentiation is altered between male and female during the formation of the ovary versus the testis. This will inform us about the causes and consequences of normal and abnormal sexual development, infertility and gonadal malignancies.Read moreRead less
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.
This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.
Testis To Ovary: Hormonal Control Of Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$803,379.00
Summary
We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide f ....We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide formation of the ovary.Read moreRead less
The Role Of Growth Differentiation Factor 9 (GDF9) In Human Fertility
Funder
National Health and Medical Research Council
Funding Amount
$568,811.00
Summary
IVF comes at a substantial financial burden to the Australia health system through Medicare. There is mounting evidence to suggest that egg quality is the key limiting factor in female fertility. The aim of this proposal is to produce a key egg-secreted protein which is critical for the ability of the egg to be fertilized and to develop a diagnostic assay to measure egg quality to improve the treatment of infertility.