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.
EGF Peptide Signalling Improves Oocyte Maturation And Quality
Funder
National Health and Medical Research Council
Funding Amount
$586,891.00
Summary
Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have developed significant new insights into mechanisms regulating egg quality. These insights have allowed us to develop a new approach to infertility treatment - crucially, one that eliminates the need for ovarian hormone therapy used in IVF. This project will investigate the basic mechanisms underlying our new approach to enable safe clinical ....Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have developed significant new insights into mechanisms regulating egg quality. These insights have allowed us to develop a new approach to infertility treatment - crucially, one that eliminates the need for ovarian hormone therapy used in IVF. This project will investigate the basic mechanisms underlying our new approach to enable safe clinical implementation.Read moreRead less
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have made significant advances towards developing new technologies that can mature eggs and produce embryos in vitro, but without women receiving hormone injections. This project will seek means to combine the benefits of two of our existing technologies into one integrated system, to provide hormone-free infertility treatment.
UNDERSTANDING THE BENEFITS AND LIMITATIONS OF METAPHASE II SPINDLE TRANSFER
Funder
National Health and Medical Research Council
Funding Amount
$1,629,373.00
Summary
Mitochondrial DNA (mtDNA) diseases are transmitted from a mother's eggs to her children. However, the levels of affected mtDNA differ amongst her eggs. Consequently, a carrier would not know if the newborn child were to suffer from these diseases. Mitochondrial Donation offers couples the potential to have an unaffected child. We will undertake the most comprehensive study of mitochondrial donation using one of its associated approaches to determine if it produces healthy embryos and offspring.
A Media Formulation To Improve Implantation Rates And Pregnancy Outcome Following ART
Funder
National Health and Medical Research Council
Funding Amount
$304,380.00
Summary
Since women are delaying childbearing, ART is increasingly required. 2-3% of births in Australia follow ART. Only 15-40% of embryo transfers in assisted reproduction (ART) result in ongoing pregnancies. The poor success rate is due to the fact that the embryo culture media bear no resemblance to the maternal environment in which they grow normally. The new culture media to be validated in this proposal includes factors that are critical for embryo implantation and will improve ART success.
Improving Oocyte Mitochondrial DNA Copy Number To Enhance Female Reproductive Capacity.
Funder
National Health and Medical Research Council
Funding Amount
$670,867.00
Summary
Eggs with too few copies of mitochondrial DNA either fail to fertilise or arrest during early development. By supplementing eggs with mitochondrial DNA, we have been able to enhance embryo quality and gene expression profiles. By breeding the offspring derived from eggs given mitochondrial supplementation, we will determine if they and their progeny meet normal developmental milestones, regulate the transmission of mitochondrial DNA appropriately, and are healthy and fertile.
Media Formulations To Enhance Embryo Formation In Assisted Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$660,133.00
Summary
The increasing age of parenthood has led to an explosion in the demand for assisted reproductive technologies such as in vitro fertilisation (IVF). This procedure has a poor success rate and is limited by the ability of fertilised eggs to mature into early embryos in the lab prior to being transferred into women. We will develop new compounds that improve embryo growth in the clinic, which will improve IVF success rates.
Periconceptual Foundations For A Healthy Start To Life.
Funder
National Health and Medical Research Council
Funding Amount
$11,022,802.00
Summary
Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions i ....Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions including heart disease, diabetes, obesity and stroke. These adverse events originate in the way that eggs and sperm develop, the uterus is prepared for implantation, the attachment of the early embryo to the lining of the uterus and subsequent growth of the placenta. This Program will study the early life events that promote or limit development of a baby's true potential for successful and healthy life. A better understanding of how lifestyle and environment interact with genes and biology to facilitate optimal growth of the fetus will underpin new preventative measures and therapeutic treatments for infertility, miscarriage and other reproductive disorders. The knowledge gained will inform health policy and clinical practise to improve reproductive health in all Australian women and promote healthy development in all Australian children. The team of researchers is a world-class group of clinicians, scientists and epidemiologists who have made major contributions to our understanding of this area. This team will interface with clinics and hospitals that engage with women prior to and during pregnancy, while having the influence to alter clinical and health practices as well as public health policies. The team will utilize the latest, most technologically advanced laboratory methods and clinical skills, including gene profiling, imaging of early pregnancy, randomised clinical trials and access to the best epidemiological and statistical assessments.Read moreRead less
The Functional Roles Of ADAMs In The Regulation Of Embryo Implantation.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
The initiation of pregnancy in humans and rodents hinges upon the ability of the embryo to attach to the wall of the uterus and invade into the uterine tissue. This process of embryo implantation is tightly regulated and depends on the secretion of enzymes and regulators of these enzymes. A newly identified family of enzymes which might be important in this process is the ADAMs family. These enzymes have the potential to facilitate both cell attachment and cell invasion and also to activate othe ....The initiation of pregnancy in humans and rodents hinges upon the ability of the embryo to attach to the wall of the uterus and invade into the uterine tissue. This process of embryo implantation is tightly regulated and depends on the secretion of enzymes and regulators of these enzymes. A newly identified family of enzymes which might be important in this process is the ADAMs family. These enzymes have the potential to facilitate both cell attachment and cell invasion and also to activate other enzymes and growth factors. Recent studies in our laboratory have shown the ADAMs to be expressed both at the most invasive time of implantation and when invasion is being down-regulated. This project will examine the role of the ADAMs in embryo implantation facilitating attachment and invasion into the uterus by acting enzymatically on the uterine tissue and by activating other enzymes. It will also determine the role of ADAMs in down-regulating invasion potentially by activating a growth factor, TNF-alpha. Knowledge of this process and particularly its regulation is important for the treatment of pregnancy associated diseases that arise from improper implantation. These include infertility, placenta accreta, choriocarcinoma, miscarriage and pre-eclampsia. Furthermore, an understanding of the regulation of implantation will contribute to the treatment of other conditions associated with cell invasion such as cancer metastasis.Read moreRead less