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.
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.
Macrophages In Developmental Programming Of Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$532,386.00
Summary
Programming of reproductive health in women begins long before sexual maturity. Development during childhood, puberty and adulthood produces a fully functional reproductive system capable of conceiving, gestating and nurturing a child. This project will investigate the role of immune cells known as macrophages in the reproductive system, and investigate how their disruption might influence developmental programming and have lifetime consequences for the reproductive health of the individual.