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.
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.
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.
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.
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.
Progenitor Origin And Regulation In Endometrial Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$847,583.00
Summary
The endometrium is the lining of the uterus and regenerates each month during a woman's reproductive years. Stem and progenitor cells in the endometrium are thought to be responsible for this regeneration. We have identified a genetic marker for stem and progenitor cells in the endometrium of mice and will use this to understand endometrial regeneration. This work will address infertility as well as overactive endometrial growth in diseases such as endometriosis and endometrial cancer.
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.
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.
Endometriosis: Defining Mechanisms For Novel Risk Loci On Chromosomes 7p15.2 And 1p36
Funder
National Health and Medical Research Council
Funding Amount
$613,124.00
Summary
We recently identified two novel genomic regions with robust evidence for associaiton with endometriosis. The result does not give immediate insights into the genes or pathways contributing to disese because the genes in each region assocaited with increased risk need to be clearly identified. This project aims to find the gene or genes responsible in each region to help develop reliable disease biomarkers and effective preventative and therapeutic strategies for this important disease.
Differential Regulation Of Endometrial Gene Expression In Endometriosis And Disease Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$163,276.00
Summary
The endometrium or tissue lining the inside of the uterus is important in implantation and pregnancy, and is implicated in diseases including endometriosis. This project aims to use RNA sequencing to provide a detailed picture of gene expression in the endometrium and combine these results with our existing data to examine genetic control of gene regulation around the time of implantation and in regions of the genome associated with endometriosis and other diseases.