The Formation And Development Of The Ovarian Follicular Membrana Granulosa
Funder
National Health and Medical Research Council
Funding Amount
$351,575.00
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 in the process of growing to ovulatory size. This project will examine the structure of the follicle wall and the cells that make up that wall. How these cells replicate during follicle growth has never been discovered. This research 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
Growth Factors And Regulatory Genes Controlling Male Spermatogonial Proliferation And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$354,536.00
Summary
In newborn and prepubertal boys the testis contains germ cells which are at a premature stage of development and very suseptible to degeneration especially if the testes fail to descend to the scrotum. The molecules which are responsible for the health of these germ cells have been unknown and only recently the way has been opened for direct study of these factors. This has been made possible by a new assay, developed in our labarotory, in which we can grow these germ cells under defined conditi ....In newborn and prepubertal boys the testis contains germ cells which are at a premature stage of development and very suseptible to degeneration especially if the testes fail to descend to the scrotum. The molecules which are responsible for the health of these germ cells have been unknown and only recently the way has been opened for direct study of these factors. This has been made possible by a new assay, developed in our labarotory, in which we can grow these germ cells under defined conditions. This step forward has highlighted some areas of knowledge which need further research such as identification of the processes which stimulate gonocytes to grow and divide. We need to test growth factors, somatic cell factors and also isolate new genes which are associated with germ cells and their growth. This knowledge will have outcomes in two major areas. First, the new findings could be applied to treatment of infertility resulting from undescended testes in which a stimulus could be given to make the germ cells grow again. Second, work in developing longer term culture of germ cells coupled with introduction of mutations will enable us to make mutant mice with a specific gene abnormality, similar to transgenic or gene knockout mice. This technological development would prove less expensive and time consuming with more reproducible and direct outcomes. Mutant mouse technology is a powerful tool to determine the effects of individual genes in the whole animal (mouse).Read moreRead less
Neuroendocrine Mechanisms By Which Leptin Regulates Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not k ....The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not known. Leptin is a hormone that is produced by fat and acts on the brain. This appears to be one of the means by which the reproductive system is regulated. Leptin also regulates food intake and other brain processes. Leptin acts on specific cell types in the brain. Some of these may have dual function to regulated appetite as well as reproduction. The present proposal is for work to determine mechanisms within the brain that are altered by leptin. We will also determine which specific mechanisms relate to the regulation of gonadotropin releasing hormone. The work will provide information on how putative appetite regulators might affect the reproductive axis. Such work will provide a platform for design of pharmaceutical means to manipulate the reproductive axis and will impact on the design of drugs that regulate obesity. It is possible that drugs that developed to control obesity may affect the reproductive axis and the project will identify these.Read moreRead less
Characterisation Of The Pathways Leading To DNA Demethylation In The Embryo.
Funder
National Health and Medical Research Council
Funding Amount
$634,573.00
Summary
Complex living creatures like humans have specialised cells that co-operate to form important organs like brains and reproductive organs. Specialised cells have specific genes locked on or off. When a sperm fertilises an egg, all the switches of the genes that are locked on or off get reset to neutral so that the fertilised egg can divide and grow into all cell types in the body. We do not know how this resetting happens in the egg. This project seeks to discover the mechanism involved.
Isolation And Function Of Human Oogenesis Genes Regulating Meiosis, Recruitment, Growth And Maturation Of The Oocyte.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes ....Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes that form the follicles containing the developing germ cells and the matured oocytes needed for IVF. The cohort of oocytes that can be harvested from any patient depends on unknown recruitment processes initiating development of a subset of the quiescent germ cells and happens in an unregulated and spontaneous manner. The present project will identify the known and unknown genes involved in recruitment of oocytes from the basal primordial population. These genes will become candidates for aiding infertile women, improving their response to fertility drugs, the development of novel contraceptive methods and potentially increasing the reproductive life span of women. Knowledge of the genes expressed in oocytes matured in vivo and in vitro will have an important bearing on the long-term opportunity to use fertility drugs in vitro instead of administration to patients for IVF. This would dramatically reduce the cost of IVF and the side-effects of hyperstimulation of ovaries of patients and the associated sequelae. The research project is a discovery program leading to the identification of the genes that govern oogenesis in the human. It is only recently that techniques have been developed to sufficient sensitivity to detect the small quantities of RNA proceeded by active genes in the individual germ cells and oocytes.Read moreRead less