Re-energising The Preimplantation Embryo To Extend Lifetime Health
Funder
National Health and Medical Research Council
Funding Amount
$1,156,936.00
Summary
Diseases of aging are associated with shortening at the ends of chromosomes called telomeres. The length of an individual’s telomeres is established during embryo development, and in situations where embryo development is compromised such as with maternal obesity the normal process of telomere lengthening may not occur. We will determine how such disruptions in embryo telomere lengthening contribute to poor health in adulthood and test ways to restore the natural process.
Optimising Female Fertility: Controlling Ovulation And Promoting Embryo Developmental Potential
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
A good quality egg at the right time is required to make a healthy embryo, influencing its lifetime health trajectory. My research aims to determine how the female ovary produces a good quality egg and releases it at the right time. This is essential for improving reproductive health in women and will identify how maternal health influences egg quality and the earliest stages of embryo growth, providing the healthiest start to life.
Metabolic And Molecular Basis Of Embryo Signalling
Funder
National Health and Medical Research Council
Funding Amount
$409,836.00
Summary
Cells in the body are powered by mitochondria that essentially generate the energy required for development. This grant will determine how the environment affects the mitochondria in the developing embryo and determine the impacts to the embryo and pregnancy if a mitochondria is partially shut down.
The Legacy Of The Egg: How Maternal Factors Set Offspring Health And Lifecourse Potential
Funder
National Health and Medical Research Council
Funding Amount
$697,605.00
Summary
Before an oocyte is fertilised, it contains all the material needed to form an embryo, and a legacy of information about its environment. My research aims to discover how oocyte signals, accumulated before conception, determine the health of the future individual; and then harness this knowledge to improve female reproductive health and generate new approaches to treat infertility and to optimise healthy embryo development in all pregnancies.
It is clear that the health and disease burden of offspring can be programmed by events before birth. This project will answer questions as to how this programming occurs. My focus is to understand how the environment affects the oocyte, sperm and embryo and how this impacts on the offspring. We will specifically study the effects of obesity and nutritional status of the parents but also the in vitro environment with a view to improving IVF outcomes.
The Negative Transgenerational Impacts Of Paternal Obesity Are Inherited Through Aberrant Methylation And MicroRNA Conetent Of Germ Cells.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
We have shown that obese fathers have reduced sperm function that negatively impacts upon their offspring’s health. But we do not understand the underlying alterations to sperm DNA that cause offspring to inherit poor health from an obese father, and whether these offspring also exhibit the same alterations. My project aims to identify alterations made to sperm DNA and RNA caused by obesity that are inherited by the next generation, ‘programming’ them for poor metabolic and reproductive health.
The Obesity Prone Oocyte- Causes, Consequences, Treatments
Funder
National Health and Medical Research Council
Funding Amount
$516,159.00
Summary
Obesity is perpetuated from mothers to offspring, in part due to changes in the oocyte (egg) that affect embryo growth. We have discovered that obesity causes changes in the mitochondria (the energy producers) of the egg. We hypothesise this causes long-lasting changes to embryo metabolism and will test, in mice, novel treatments to reverse the detrimental effects. The project will show how obesity affects embryo metabolism and growth, and determine whether defects can be prevented by drugs or l ....Obesity is perpetuated from mothers to offspring, in part due to changes in the oocyte (egg) that affect embryo growth. We have discovered that obesity causes changes in the mitochondria (the energy producers) of the egg. We hypothesise this causes long-lasting changes to embryo metabolism and will test, in mice, novel treatments to reverse the detrimental effects. The project will show how obesity affects embryo metabolism and growth, and determine whether defects can be prevented by drugs or lifestyle changes.Read moreRead less
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
Obesity And Infertility: Effects Of Diet-induced Insulin Resistance On Oocyte Quality.
Funder
National Health and Medical Research Council
Funding Amount
$533,510.00
Summary
The health of an embryo (and subsequently child) is largely determined by the health of the mother. It is well documented that women who have poor pre-pregnancy health due to obesity are more likely to have difficulty conceiving due to irregular ovulations and early embryo loss. My research using obese mice has found that these fertility problems are partly due to alterations in the oocytes (eggs) within the ovary. Its surrounding cells and fluid provide the oocyte with all of its required nutri ....The health of an embryo (and subsequently child) is largely determined by the health of the mother. It is well documented that women who have poor pre-pregnancy health due to obesity are more likely to have difficulty conceiving due to irregular ovulations and early embryo loss. My research using obese mice has found that these fertility problems are partly due to alterations in the oocytes (eggs) within the ovary. Its surrounding cells and fluid provide the oocyte with all of its required nutrients. I hypothesize that this follicular environment is altered in females that are obese leading to inappropriate nutritional signals and suboptimal development of the oocyte. The goals of my research are to use obese mice to 1) pinpoint exactly which metabolic alterations lead to decreased oocyte development; 2) determine how these metabolic alterations change the oocyte and the cells surrounding it; 3) use the information gained to analyse ovarian cells of women and see if these same alterations occur in women who are obese. The findings will be highly significant because they will 1) provide a greater understanding of how the maternal environment communicates nutritional information to the oocyte, which ultimately forms the developing embryo. 2) expand our knowledge of the optimal nutritional conditions for oocyte and early embryo development. 3) identify biological mechanisms that are altered during obesity and lead to decreased female fertility. 4) aid in the development of improved agents for use at fertility clinics, for instance the development of solutions most closely mimicking the critical components of the normal ovarian environment, for use in the culture of oocytes and embryos. 5) provide a strong public health message to women of reproductive age: to achieve and maintain a healthy body weight prior to becoming pregnant.Read moreRead less