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
I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
A New Model Of Asthenospermia And A Candidate Gene For Multiple Ciliopathies
Funder
National Health and Medical Research Council
Funding Amount
$629,039.00
Summary
Though the analysis of a unique mouse strain (Mot1) we have identified a previously unknown cause of male infertility and lung disease. We hypothesis that the Mot1 line is a model of human primary cilia dyskinesia and that the Mot1 protein is involved in cilia function. Within this project we will define the consequences of a loss of Mot1 protein function, we will define its binding partners and we will screen for mutations in the corresponding human gene.
Effects Of Leptin On Follicle Growth And Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$196,470.00
Summary
Leptin is a recently discovered hormone which is very important in controlling body weight. Extremely obese, or extremely underweight women, find it difficult to become pregnant, and leptin is probably the connection between weight and fertility. This may be a particularly important factor in polycystic ovary syndrome (PCOS), a distressing condition which affects 5% of women and causes both obesity and infertility. Exciting new research suggests that leptin also affects the immune system, and pr ....Leptin is a recently discovered hormone which is very important in controlling body weight. Extremely obese, or extremely underweight women, find it difficult to become pregnant, and leptin is probably the connection between weight and fertility. This may be a particularly important factor in polycystic ovary syndrome (PCOS), a distressing condition which affects 5% of women and causes both obesity and infertility. Exciting new research suggests that leptin also affects the immune system, and previous NH and MRC funding has enabled us to demonstrate that the immune system plays a crucial role in maintaining normal ovarian function. The nutritional status of the body, the immune system and the reproductive system all interact, and leptin appears to be the connecting link between these three major systems. We propose that leptin plays a major role in the ovary, and wish to determine how leptin mediates the effects of bodyweight and the immune system on ovarian function. Laboratory rats will be treated with leptin, their food intake and weight recorded, and a few weeks later the rats will have their ovaries removed. We will find out whether ovaries respond to leptin, or whether the ovarian response changes according to the menstrual cycle: perhaps leptin is very important just before ovulation, but it does not affect menstruation? Do any ovarian cells make leptin? Will leptin stimulate ovaries to produce more oestrogen or progesterone, or ovulate more eggs? We will also identify immune system cells in the ovary, and note whether leptin affects them. We will be able to relate all this data to weight and diet. Increased understanding of leptins' effect on the ovary has the potential to lead to new, improved treatments for PCOS or for unexplained cases of infertility. It is also possible that in the future a weight-loss regime might be developed which takes a womans monthly cycle into account, therefore making weight-loss more efficient and attainable.Read moreRead less
Mechanisms of manchette function. This project aims to define the function of the manchette, a poorly understood microtubule-based structure present in haploid male germ cells. This project aims to define key mechanisms underpinning manchette development and movement, and to generate a detailed picture of the dynamics of germ cell development using imaging technologies and unique animal models. Such knowledge should improve the understanding of how male fertility is achieved, the origin of infer ....Mechanisms of manchette function. This project aims to define the function of the manchette, a poorly understood microtubule-based structure present in haploid male germ cells. This project aims to define key mechanisms underpinning manchette development and movement, and to generate a detailed picture of the dynamics of germ cell development using imaging technologies and unique animal models. Such knowledge should improve the understanding of how male fertility is achieved, the origin of infertility and how species-specific differences in sperm form are achieved. Such insights may ultimately lead to improved agricultural efficiencies and job creation.Read moreRead less
Maximizing male fertility: the role of CRISP proteins. This project aims to investigate the function of cysteine rich secretory protein (CRISP) family members in fertility. It is expected to generate new knowledge on the role CRISP1 and 4 play in sperm competition in vivo, and thus, evolutionary processes; to define the role seminal plasma CRISPs play in fertility; and identify the mechanism underpinning their biological activities. This will be achieved using a range of innovative, state-of-the ....Maximizing male fertility: the role of CRISP proteins. This project aims to investigate the function of cysteine rich secretory protein (CRISP) family members in fertility. It is expected to generate new knowledge on the role CRISP1 and 4 play in sperm competition in vivo, and thus, evolutionary processes; to define the role seminal plasma CRISPs play in fertility; and identify the mechanism underpinning their biological activities. This will be achieved using a range of innovative, state-of-the-art approaches. Expected outcomes and benefits include an enhanced knowledge of the mechanisms underpinning fertility and infertility, enhanced collaboration and research knowhow, and an evidence base for future applied projects aimed enhancing fertility in agricultural species.Read moreRead less
Improving the efficiency of bovine oocyte maturation in vitro. For the dairy and beef industries, the hundreds of eggs (oocytes) in a high value cow's ovary that fail to produce a pregnancy are a wasted genetic resource. A key technology to unlocking this resource is in vitro maturation of oocytes, but the process is inefficient. One possible cause is that the current approaches to maturing oocytes in vitro do not adequately mimic the natural process in vivo. We will design new systems to matu ....Improving the efficiency of bovine oocyte maturation in vitro. For the dairy and beef industries, the hundreds of eggs (oocytes) in a high value cow's ovary that fail to produce a pregnancy are a wasted genetic resource. A key technology to unlocking this resource is in vitro maturation of oocytes, but the process is inefficient. One possible cause is that the current approaches to maturing oocytes in vitro do not adequately mimic the natural process in vivo. We will design new systems to mature cow oocytes in vitro by altering the chemical composition of maturation medium, thus improving the efficiency of laboratory embryo production and related technologies.Read moreRead less
Dissecting the impact of stress on reproduction: Novel peptide mediates inhibitory effects of stress on female reproduction. This research proposal offers a pioneering opportunity to develop treatments that overcome the negative impact of stress on reproduction. Specifically, knowledge generated in this project will be vital in the development of strategic defences against the impact of stress on reproduction. This project fundamentally addresses Research Priority 2: Promoting and maintaining go ....Dissecting the impact of stress on reproduction: Novel peptide mediates inhibitory effects of stress on female reproduction. This research proposal offers a pioneering opportunity to develop treatments that overcome the negative impact of stress on reproduction. Specifically, knowledge generated in this project will be vital in the development of strategic defences against the impact of stress on reproduction. This project fundamentally addresses Research Priority 2: Promoting and maintaining good health. Given that suppression of reproduction by stress occurs in all mammalian species including humans, domestic animals and wildlife, being able to prevent or overcome stress-induced reproductive dysfunction will generate significant health, social, economic and ecological benefits. Read moreRead less
The impact of environmental toxicants on the fertility of female animals. This study aims to address a problem of national significance; determining the impact of commonly used environmental toxicants (pesticides) on the fertility and health of female animals, both agricultural and native. This project expects to generate new knowledge in the fields of ovarian biology, female fertility and toxicology by using a combination of mouse and marsupial animal models. The expected outcomes include the e ....The impact of environmental toxicants on the fertility of female animals. This study aims to address a problem of national significance; determining the impact of commonly used environmental toxicants (pesticides) on the fertility and health of female animals, both agricultural and native. This project expects to generate new knowledge in the fields of ovarian biology, female fertility and toxicology by using a combination of mouse and marsupial animal models. The expected outcomes include the establishment of interdisciplinary collaborations and provision of world-class training for staff and students in the field of reproductive biology. This project should provide significant benefits, such as improved chemical management in livestock production and the development of marsupial conservation action plans.Read moreRead less