Therapeutic Potential Of Transforming Growth Factor-beta Proteins For The Diagnosis And Treatment Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$942,961.00
Summary
We discovered and manufactured a growth factor produced uniquely by the egg. We named this growth factor cumulin. It is a powerful regulator of ovarian function and egg quality. This project will study the basic mechanisms of how cumulin works in the ovary. We will then develop an assay to measure it as a biomarker of human egg quality and quantity. New approaches in fertility preservation for cancer survivors will be developed using cumulin.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
Dr Gilchrist is a reproductive biologist studying factors that regulate the intrinsic quality of unfertilised eggs. He has developed a new form of hormone-free infertility treatment which he will test in a clinical trial over the next 5 years.
The Importance Of The Blood-testis Barrier In Human Infertility
Funder
National Health and Medical Research Council
Funding Amount
$560,953.00
Summary
The blood-testis barrier (BTB) shields developing sperm from the circulation and immune system, which would see them as ‘foreign’. Loss of BTB function leads directly to infertility. Curiously, how the BTB ‘opens’ and ‘closes’ to allow entry without causing a ‘leak’ is unknown. We believe that activin A is the main gatekeeper, but this growth factor is also important in inflammation. Our goals are to show how activin A allows sperm cells entry, and how inflammatory diseases impact the BTB.
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
The Role Of Transcription Factors In Regulating The First Round Of Gene Expression In The Early Embryo.
Funder
National Health and Medical Research Council
Funding Amount
$348,931.00
Summary
Assisted reproductive technologies result in a high incidence of multiple births. This is and adverse outcome that requires correction. It stems from the common transfer of several embryos due to the low chance of an individual embryo made by IVF resulting in a baby. This project will determine the normal pattern of gene expression in the embryo and define: (1) how it is adversely changed as a consequence of IVF; and (2) the extent that these changes are a cause of the low embryo viability.
Mechanisms Of P53 Induced Embryopathy After In Vitro Fertilisation.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
Assisted reproductive technologies (ART) cause many embryos not to survive to birth. We have shown that IVF causes increased expression of protein normally involved in stopping cells from dividing. This is a major cause of embryo death after IVF. This project will determine how this protein acts to cause embryonic death and assess strategies to prevent it.
GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.