Kisspeptin And Its Receptor Mastermind Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Reproduction is controlled by the brain and gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. Finding critical regulators of GnRH has remained the most important goal for reproductive endocrinologists for over 30 years. The brain peptide hormone called kisspeptin and its receptor Kiss1R appear vital in the control of reproduction. This project will detail the role kisspeptin and Kiss1R play in controlling hormones from the brain that govern puberty and reproduction.
Role Of Mouse Rad21 And Rec8 Genes In Recombination And Ionising Radiation Response
Funder
National Health and Medical Research Council
Funding Amount
$403,750.00
Summary
We have created a line of mice and are creating a second mouse line which lack two specific genes known as Mrec8 and Mrad21. These genes have a number of roles in mammals. These roles include acting as a glue to hold chromosomes together and allowing exchange of DNA between separate DNA molecules. The latter is important in physiological processes such as genetic exchange during meiosis, but also in the response of the cell to DNA damage, specifically, breakages in both strands of the DNA helix. ....We have created a line of mice and are creating a second mouse line which lack two specific genes known as Mrec8 and Mrad21. These genes have a number of roles in mammals. These roles include acting as a glue to hold chromosomes together and allowing exchange of DNA between separate DNA molecules. The latter is important in physiological processes such as genetic exchange during meiosis, but also in the response of the cell to DNA damage, specifically, breakages in both strands of the DNA helix. In the studies proposed here, we will breed these mice both with each other and with other mice that have specific, single gene defects which lead to abnormal responses to DNA strand breakages. We shall assess the effects of the different genes on response to DNA strand breaking agents in the animals, as well as in cells which have been derived from the animals. These experiments are expected to shed light onto the consequences of defects in DNA repair for the stability of cells and animals, and may provide information which ultimately benefits cancer patients, especially those having radiotherapy.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
Transplantation of frozen ovarian tissue is being used by young patients at risk of losing ovarian function. This study aims to maximize the likelihood that patients who have ovarian tissue collected, frozen and returned will acheive the desired outcome of returning ovarian hormonal cyclicity, ovulation, or fertility.
Novel Analogues Of Human INSL3 As Antagonists And Probes Of Testicular Function
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
The hormone, insulin-like peptide 3, has recently been shown to act directly on male and female germ cells to cause their maturation. It has considerable promise as a therapeutic agent for the regulation of fertility. Drugs based on the peptide may be used to assist in cases of infertility, and drugs that block its action have great potential as male and female contraceptives. Towards these goals, our project aims to understand how this peptide exerts its unique biological effects.
Mechanisms Of Negative Feedback Regulation Of GnRH By Testosterone In Males
Funder
National Health and Medical Research Council
Funding Amount
$243,336.00
Summary
This project will improve our knowledge of the hormonal control of reproduction in males. The hormone testosterone, produced by the testes, acts on the brain to control the secretion of a substance called gonadotrophin releasing hormone (GnRH). GnRH acts on a small gland at the base of the brain to cause the production of hormones called gonadotrophins, that are essential for reproduction. These gonadotrophins act on the testes to ensure the production of sperm and other hormones, including test ....This project will improve our knowledge of the hormonal control of reproduction in males. The hormone testosterone, produced by the testes, acts on the brain to control the secretion of a substance called gonadotrophin releasing hormone (GnRH). GnRH acts on a small gland at the base of the brain to cause the production of hormones called gonadotrophins, that are essential for reproduction. These gonadotrophins act on the testes to ensure the production of sperm and other hormones, including testosterone. We plan to determine how testosterone acts on the brain to control GnRH secretion. To do this we will use male sheep and conduct a series of experiments designed to show where in the brain testosterone acts to ultimately affect the nerve cells that produce GnRH. Testosterone and similar compounds are increasingly being used as treatments for infertility, as a male contraception and misused as anabolic steroids. A thorough knowledge of how testosterone acts in the brain is necessary to improve treatments for reproductive disorders and ultimately to improve reproductive health in men.Read moreRead less
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
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.
Characterization Of The Molecular Basis Of Human Sperm-oocyte Interaction
Funder
National Health and Medical Research Council
Funding Amount
$492,956.00
Summary
In this proposal, we shall exploit our expertise in gamete biology and innovative proteomic technologies to elucidate the molecular mechanisms that underpin human sperm-oocyte interaction. This exquisitely cell- and species-specific event constitutes one of the most strategically important cellular interactions. Our research will provide the foundation for diagnosis and treatment of male infertility and identify a range of targets for the development of novel contraceptive technology.
Epithelial-trophoblast Interactions In Human Embryo Implantation: Role For Interleukin 11 And Leukemia Inhibitory Factor
Funder
National Health and Medical Research Council
Funding Amount
$495,667.00
Summary
Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Female infertility is frequently due to implantation failure and many IVF embryos fail to implant. Appropriate development of the placenta is critical to the outcome of pregnancy and inadequate placentation can result in spontaneous abortion. However, if the pregnancy continues with a poorly developed placenta, the mother is likely to develop pre-eclampsia with subsequent major adverse outcomes for both mother and b ....Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Female infertility is frequently due to implantation failure and many IVF embryos fail to implant. Appropriate development of the placenta is critical to the outcome of pregnancy and inadequate placentation can result in spontaneous abortion. However, if the pregnancy continues with a poorly developed placenta, the mother is likely to develop pre-eclampsia with subsequent major adverse outcomes for both mother and baby. Pre-clampsia is the most common cause of low birth weight infants and also of maternal death. Low birth weight, which is commonly an outcome of a pregnancy with pre-eclampsia, correlates with disorders later in life (including hypertension, diabetes, coronary heart disease and obesity). Interleukin (IL)-11 and leukemia inhibitory factor (LIF) are among very few molecules known to be critical for embryo implantation in the mouse. Their roles in human infertility are not well understood, although there is evidence that decreased LIF is associated with implantation failure in women. The distribution of these molecules within the uterus and placenta in primates suggests they have important roles in preparing the uterine lining for implantation and for development of a placenta in women. This project will examine how IL-11 and LIF that are locally produced at implantation sites affect the human uterus and the formation of the placenta. There is still no means of readily diagnosing endometrial infertility in women or of establishing whether the placenta is developing adequately. These studies will provide new critical information regarding the roles of these two molecules and their potential usefulness as targets for much- needed diagnostic and therapeutic tools for infertility and major diseases associated with pregnancy. Application of such new tests will produce lifelong benefits to the health of both the mother and child.Read moreRead less