The Mechanism Of Spermatid Differentiation - A Link To Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$506,425.00
Summary
To discover novel regulators of male fertility, we have screened libraries of mutant mice generated by a chemical mutagen. This project aims to define the function of the mutated gene identified in a male-specific infertile mutant mouse line. The mutated gene has been proposed to play a role in regulating cell death and suppress lung tumour formation. Our data may reveal novel options for male infertility treatment and for the development of male contraception and lung cancer biomarkers.
Role Of Tumour Suppressor Genes In Early Embryopathy
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. The high mortality of the early embryo seems to be a general feature of ART but its causes and effectors are incompletely defined. It has been established that this high mortality is largely due to a marked retardation in ....Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. The high mortality of the early embryo seems to be a general feature of ART but its causes and effectors are incompletely defined. It has been established that this high mortality is largely due to a marked retardation in the rate of cell cycle progression by embryo cells, and commonly is associated with a form of cell 'suicide', known as apoptosis. In non-embryonic cells a group of genes known as the tumour suppressor genes (TSGs) are responsible for slowing cell-cycle progression and are commonly involved in inducing apoptosis following cell stress. The role of TSGs in the early embryo is not well studied. We have recently shown that the most important of the TSGs, P53, is normally kept at very low levels in the early embryo but that ART causes up-regulation of its expression. This upregulation is a major cause of the embryopathy associated with ART in an animal model but that genetic mutations that prevent P53 expression favours increased embryo development and viability. This project will examine whether ART also causes up-regulation other important TSGs and whether this occurs in human embryos. We will examine the hypothesis that ART increases the survival of embryos with mutations to the P53 gene (creating a postive genetic selection pressure in favour of these mutations); and which aspects of ART cause this positive selection. The project will demonstarte whether changes in the ART procedures have the potential to mitigate against selection of embryos bearing deletrious mutations.Read moreRead less
Hypospadias is one of the most common developmental defects in humans, yet over two thirds of the cases cannot be explained. Our recent studies using marsupials show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. This study will provide novel data on the interactions of the genes and hormones that will inform our understanding of this common developmental defect of male development
The Role Of Placental Transcription Factors In The Pathogenesis Of Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$601,582.00
Summary
We must understand the role of growth control genes in the growth of the human placenta. The reason is that in several significant placental disorders, placental formation is abnormal and prevents the placenta from functioning efficiently. This in turn, impacts on the growth of the developning fetus. A variety of established and innovative methods described in this project will determine the functions of the placental growth control genes and may lead to novel therapeutic targets.
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