Endometrial Receptivity For Embryo Implantation: Proprotein Convertase 6 And Plasma Membrane Remodeling
Funder
National Health and Medical Research Council
Funding Amount
$631,344.00
Summary
Implantation of an embryo into the uterus is a key step in establishing pregnancy; it requires a receptive uterus (fertile soil) and a healthy embryo (seed). Implantation failure causes pregnancy loss and infertility, and is also a major limiting factor in IVF. We have established that proprotein convertase 6 (PC6) is a master regulator of uterine receptivity for implantation. We will investigate how PC6 works in a woman’s uterus, and how we can use this knowledge to improve implantation in IVF.
The failure of an embryo to implant is a major cause of infertility. While IVF is an important intervention, still three quarters of embryos do not implant. We have identified new factors that we believe are critically important in embryo attachment to the womb. We will now prove whether these factors are critical and therefore provide the evidence required to begin to develop novel treatment options for infertility.
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.
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.
Failure-to-progress In Human Labour Results From A Profound Electrical Negativity Of The Uterine Cells: Targeting The Ion Channels Involved
Funder
National Health and Medical Research Council
Funding Amount
$564,541.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems to lay the foundations for better therapeutics.
Embryo implantation is a critical step in establishing pregnancy, requiring stable attachment of an embryo to the uterus. For this to occur, the embryo must be implantation competent and the uterus must be receptive. However, to date, little is known about the interactions between the two that determine a successful implantation in the human. This project will investigate a novel embryo-derived enzyme that drives human implantation. These studies are important to improve infertility treatment.
Facilitating Endometrial Receptivity To Improve Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$734,252.00
Summary
The womb prepares itself in each menstrual cycle for pregnancy and the implantation of an embryo. In some women, the endometrium may not prepare itself adequately and this can lead to infertility. We have identified small RNA that may be useful in predicting which women are not adequately prepared for implantation and may be used to develop treatments for infertile women, for which there are currently no treatments.
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.
Menstrual Fluid Factors In The Control Of Progestin Mediated Endometrial Bleeding
Funder
National Health and Medical Research Council
Funding Amount
$379,845.00
Summary
Uterine bleeding associated with progestin-only contraceptives is the main reason for discontinuation of these highly effective items. For bleeding to occur the endometrial blood vessels and overlying epithelium must undergo simultaneous breakdown. We do not know the mechanism behind breakdown under progestin exposure. We propose novel directions to understand the molecular cues underlying epithelial fragility/breakdown and novel treatments to stop bleeding thus enhancing contraceptive complianc ....Uterine bleeding associated with progestin-only contraceptives is the main reason for discontinuation of these highly effective items. For bleeding to occur the endometrial blood vessels and overlying epithelium must undergo simultaneous breakdown. We do not know the mechanism behind breakdown under progestin exposure. We propose novel directions to understand the molecular cues underlying epithelial fragility/breakdown and novel treatments to stop bleeding thus enhancing contraceptive compliance.Read moreRead less
Identification And Function Of Genes That Increase Risk For Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$1,180,912.00
Summary
Endometriosis is a common disease that affects 7% of reproductive age women in Australia, resulting in pelvic pain, subfertility and painful periods. We have undertaken genetic studies that identified a number of candidate genes that show strong evidence for increasing a woman’s risk of having endometriosis. We now seek funding to investigate the functional roles that these endometriosis susceptibility genes play within the uterus, with the goal of identifying new treatments for endometriosis.