Risk Of Birth Defects In Children Born Following Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$191,962.00
Summary
The development of assisted reproductive technology (ART) for infertility treatment has advanced at a tremendous pace since late 1970's. The use of ART is becoming increasingly frequent, with Australia having one of the highest rates of use internationally. Over 4,000 births result from ART annually in Australia. At the same time, minimally invasive infertility treatment-ovulation induction and insemination, remains a main option for some infertile couples and also generates several thousand bir ....The development of assisted reproductive technology (ART) for infertility treatment has advanced at a tremendous pace since late 1970's. The use of ART is becoming increasingly frequent, with Australia having one of the highest rates of use internationally. Over 4,000 births result from ART annually in Australia. At the same time, minimally invasive infertility treatment-ovulation induction and insemination, remains a main option for some infertile couples and also generates several thousand births annually. A fundamental concern for those involved in infertility treatment is the health of the children born following the treatment. Evidence from many studies indicates that compared to the general population, ART babies are more likely to be a twin or triplet, have a low birth weight, be born premature, and suffer higher rates of perinatal death and cerebral palsy. These issues are gradually being addressed by transferring a single embryo in a cycle. Of greater concern is the recent reporting by a Western Australian team that the risk of major birth defects is doubled in ART children. This is a highly significant finding that has raised concern in patients and clinicians. It is imperative to verify the findings through replication in a larger study. It is equally important to identify whether the increased risk is due to potentially modifiable treatment factors or patient factors related to their infertility. This innovative study will therefore also separate patient characteristics and type of treatment, and partition the risk attributable to various factors. The health of children from infertility treatments is of fundamental concern and has become an important public health issue. This study will direct future basic research in embryology and clinical services where there is a continual need to balance technical innovation and efficacy with treatment safety. The long-term benefit will be improvement of the health status of Australian families.Read moreRead less
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
Cohesin: Role In Germ Cell Chromosomal Segregation
Funder
National Health and Medical Research Council
Funding Amount
$435,526.00
Summary
At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related gen ....At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related genes, called Rec8 and Rad21, which we recently discovered in humans and mice. Due to that these genes are essential for chromosome separation in other species and they exists in species as diverse as yeast and humans, they may be responsible for accurate separation of chromosomes in germ cells in mammals. In this proposal, we will determine the role(s) of these molecules in controlling proper chromosome segregation by loss-of-function studies in genetically engineered mice lacking Rec8 and Rad21 genes. By analyzing the chromosomal abnormalities of the cells from these animals, we will gain critical information about the nature of chromosome partitioning disorders in humans.Read moreRead less
Inflammatory Cytokines As Causal Agents In Peri-conception Programming Of Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$604,046.00
Summary
Events at conception set the trajectory of fetal developmental that will determine health of children after birth and in later life. Susceptibility to obesity and metabolic conditions is established at this very early time. This project will define the molecular signals affecting the embryo in the event of maternal or paternal infection, diet and stress. The results will help us devise health advice for intending parents to improve child health and help prevent onset of metabolic disorders.
Understanding The Determinants Of Human Oocyte And Embryo Health
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
This project will address key questions involving how the human egg and embryo maintain their ability to develop into a healthy fetus. In recent years there have been significant advances in our understanding of how animal oocytes grow and become competent as well as an increased understanding of how the animal embryo maintains its viability in culture. Currently there is little information as to how the human oocyte and embryo develops. This study will address the current lack of knowledge by e ....This project will address key questions involving how the human egg and embryo maintain their ability to develop into a healthy fetus. In recent years there have been significant advances in our understanding of how animal oocytes grow and become competent as well as an increased understanding of how the animal embryo maintains its viability in culture. Currently there is little information as to how the human oocyte and embryo develops. This study will address the current lack of knowledge by extending the information gathered in animal models to establish how the human oocyte communicates with its surrounding cells and how this communication is important for development. We will also study how the developing embryo maintains its physiology and metabolism and the relationship between the ability to control metabolic balance and viability will be established. All of the questions outlined in this proposal can be performed without disturbing the oocyte and developing embryo by analysing the surrounding cells and the spent media. Therefore, all of these questions can be answered non-invasively. The outcome of this proposal will be an increased understanding of how the physiology and development of the human oocyte and embryo is maintained. However, importantly this data will then provide information as to the relationship of these parameters to developmental competence. Therefore, it will be possible to establish a range of markers that can be used to predict the developmental competence of a human embryo. Currently multiple embryos are routinely transferred in an IVF cycle resulting in an increase in multiple gestation pregnancies and their associated complications. The information generated in this study will provide information enabling markers to be used to identify the most viable embryo from a cohort, which is essential if single embryo transfer is to be universally adopted in an IVF program.Read moreRead less
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.
Metabolic And Molecular Determinants Of Embryo Viability
Funder
National Health and Medical Research Council
Funding Amount
$551,321.00
Summary
We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data dem ....We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data demonstrating that exposure of embryos to physiological perturbations alters fetal development, similarly to that occurring in nutrient restriction during pregnancy. Furthermore, there is data from IVF-derived children that their birth-weight is lower than expected, possibly due to the conditions used for conception in the laboratory. How does the response by eggs and embryos, at the time of conception, affect subsequent development? There has been some focus on changes to DNA that are not related to mutations, but structural changes in the DNA that alters gene expression. We call this epigenetics and epigenetic changes are found in embryos, including human embryos following IVF. However, no one knows how such epigenetic changes occur as a result of this stress response by the egg or embryo. Our proposal is to determine the mechanism of how epigenetic alterations take place in eggs and embryos. Our theory is that the mitochondria, the energy producing packages within all cells, are sending signals to the embryo's nucleus. When the egg or embryo finds itself in adverse conditions, the signals change as a result of changes in the energy balance. This in turn changes the activity of enzymes in the nucleus that regulates DNA structure. If we can prove that this relationship occurs, then we can assess these changes in human embryos that are excess to a patient's requirements and learn if programming takes place in human embryos.Read moreRead less
The normal processes of development of the embryo require that the information encoded in chromosomes be reprogrammed soon after fertilization. This process is rather fragile and disturbance of the early embryo can upset it. Recent studies for the chief investigator's provide new understanding of the normal processes of reprogramming. The project will explore and validate the implications of these new discoveries and provide a basis for future alleviation of abnormalities to development.
Identification And Characterisation Of Phosphorylation Events Taking Place During Human Sperm Capacitation
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Male infertility affects one in every twenty Australian males and one third of all infertile couples worldwide. The most common cause of human infertility is not a failure to produce sperm, but a failure of these cells to express a normal capacity for fertilization. The cause of this loss of functional competence is unclear. We are going to use our technical expertise in proteomics to characterize the molecular pathways responsible for the defective sperm function seen in infertile patients.
The Long-term Consequences Of Assisted Reproduction On The Growth, Metabolic, Respiratory, Psychological, Immunological And Reproductive Development Of The Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$1,552,096.00
Summary
1 in 25 children are born from IVF treatment - incredibly- to our shame; no data exists as to the long-term health of these children. Presented is a unique opportunity, which would be exceedingly difficult to replicate elsewhere in the world, to determine the long-term consequences of IVF upon the development of the offspring, by comparing their growth, metabolic, respiratory, psychological, immunological and reproductive development to a representative sample of WA children- the Raine cohort.