Reappraisal Of The Mechanisms Underlying Implantation Success Or Failure
Funder
National Health and Medical Research Council
Funding Amount
$750,755.00
Summary
Infertility affects 1:6 Australian couples; these seek help. However, for each IVF cycle, there is only ~18.5% chance of a live birth, significantly due to failure of embryo implantation. We discovered nano-vesicles in the uterine cavity, that are released from the womb lining and taken up by the pre-implantation embryo to improve its implantation potential. We will determine how this extracellular environment can enhance implantation success and circumvent/management of infertility.
Decidual-trophoblast Interactions Critical For Optimal Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$612,927.00
Summary
This proposal seeks to identify the critical maternal and embryonic placental factors that regulate the formation of a healthy placenta and thus a healthy pregnancy and baby. Currently there is no way of identifying whether the placenta is forming adequately. The proposed studies are a necessary first step in identifying therapeutic targets for diseases associated with a poorly formed placenta, such as preeclampsia.
Epigenetic Regulation Of Cell Lineage Differentiation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$440,983.00
Summary
Exposure of embryos to a range of stresses can increase the predisposition to chronic diseases of adulthood. Stressing embryos at critical stages of development cause errors in reorganization of the nucleus that are required for normal gene expression. These errors are propagated into adulthood. This project will map the normal processes of nuclear reorganization and define how stress to the embryo changes this process, allowing an understanding of the causes of some important chronic diseases.
Changes In Protein Glycosylation Promote Endometrial Receptivity Leading To Successful Implantation
Funder
National Health and Medical Research Council
Funding Amount
$489,198.00
Summary
~15% of couples are unable to have children. Their reliance on reproductive technologies (eg, IVF) has increased 4 fold over the past decade. One reason for infertility is that the lining of the uterus (endometrium) is not able to allow an embryo to attach – a key event in establishing healthy pregnancy. There is no test to assess whether the endometrium is ‘receptive’ to an embryo. We will develop special assays for a test and provide a basis for treatment without recourse to IVF.
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.
Endometrial Exosomes: A New Paradigm In Endometrial-embryo Cross-talk
Funder
National Health and Medical Research Council
Funding Amount
$726,978.00
Summary
Establishment of pregnancy requires molecular communication between the embryo and the lining of the womb (the endometrium) which enhances implantation into the womb and placental development. Nanoparticles (exosomes) released by the endometrium into the uterine cavity, carry cargo of genetic material and proteins, which may be transferred to the pre-implantation embryo. We will define functional changes induced by exosomes, that impact on implantation and the fetus’s long-term health.
Epigenetic Reprogramming Within The Pluripotent Lineage Of The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$663,050.00
Summary
Cells of the early embryo have the remarkable capacity to form all of the different tissues and organs in the body. This property requires re-organisation of the embryo’s genetic material in a manner analogous to re-booting a computer. This project will define the properties of this rebooting process. This information will allow much better strategies for building spare parts for regenerative medicine and provide the information required to reduce the incidence of inborn defects.
Long Term Consequences Of Perturbing Early Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$549,515.00
Summary
Assisted reproductive techniques are normally considered safe, but there are increased risks for these newborns which may be caused by these procedures. We have developed mouse models that are sensitive to these effects and have used them to show that gene expression is altered in mice that develop from cultured embryos. Now we will use these models to work out how to reduce these effects and ensure the ongoing health of babies born with assisted reproduction.
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.
Intergenerational Transmission Of Gender-specific Metabolic Disease For Offspring Born Small: Maternal, Paternal And Embryonic Roles
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
This proposal addresses the underlying metabolic health consequences of poor embryo and growth of the baby across generations. We will define mechanisms by which a poor functioning placenta during a rat mother’s pregnancy programs her offspring born small to transmit gender-specific diseases to the next generation. We will identify mechanistic pathways involved, specifically the relative contributions of maternal and paternal germ lines and adverse maternal adaptations to pregnancy for females b ....This proposal addresses the underlying metabolic health consequences of poor embryo and growth of the baby across generations. We will define mechanisms by which a poor functioning placenta during a rat mother’s pregnancy programs her offspring born small to transmit gender-specific diseases to the next generation. We will identify mechanistic pathways involved, specifically the relative contributions of maternal and paternal germ lines and adverse maternal adaptations to pregnancy for females born small.Read moreRead less