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.
Female Reproductive Health Preservation By Nicotinamide Adenine Dinucleotide (NAD+) And Sirtuin2 (SIRT2)
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Cancer treatment can be severely toxic to women’s eggs. Increasing numbers of women who survive cancer therefore become infertile and prematurely deprived of hormonal support whilst still in their reproductive years. This project will use state-of-the-art techniques to interrogate newly uncovered pathways that can protect eggs from treatment-induced injury thereby greatly improving the quality of life for female cancer survivors.
Mechanisms Of DNA Damage-induced Oocyte Apoptosis And Infertility: Examination Of The Role Of BH3-only Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$495,755.00
Summary
Our ability to prevent or postpone menopause following cancer treatment, is of great importance for female fertility, health and quality of life. We will demonstrate that the death gene of the Bcl-2 family of life and death genes, Puma, is responsible for killing female germ cells after damaging treatment. When Puma is absent, sufficient high quality germ cells are able to survive damaging treatment, allowing normal fertility in mice. The quality of these rescued germ cells will be analysed in d ....Our ability to prevent or postpone menopause following cancer treatment, is of great importance for female fertility, health and quality of life. We will demonstrate that the death gene of the Bcl-2 family of life and death genes, Puma, is responsible for killing female germ cells after damaging treatment. When Puma is absent, sufficient high quality germ cells are able to survive damaging treatment, allowing normal fertility in mice. The quality of these rescued germ cells will be analysed in detail.Read moreRead less
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.
Interferon Epsilon, A Key Cytokine In The Pathophysiology Of The Female Reproductive Tract Mucosa
Funder
National Health and Medical Research Council
Funding Amount
$793,303.00
Summary
The female reproductive tract is a complex environment, which permits pregnancy but protects against infections, all under the influence of hormones and the resident microbial flora. We have discovered a novel protein called interferon epsilon that acts on cells in the female reproductive tract to regulate protection against infections. We aim to discover how this new protein works and will determine its therapeutic potential in infections and inflammatory diseases affecting women's health.
Male-female Sperm Signalling - A Novel Pathway For Peri-conceptual Health?
Funder
National Health and Medical Research Council
Funding Amount
$674,920.00
Summary
This project will investigate a new biological process in reproduction, whereby sperm delivered to the cervix at coitus transmit signalling molecules called microRNAs that influence the female immune response, to increase the chances of conception and pregnancy. We will define the molecular details of this signalling pathway in mouse models, and then determine whether human sperm have a comparable function in ‘priming’ the female body to conceive.
Proprotein Convertase 6: A Master Regulator For The Development Of Endometrial Receptivity And Embryo Implantation
Funder
National Health and Medical Research Council
Funding Amount
$424,846.00
Summary
Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in sponta ....Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in spontaneous abortion. How the uterus becomes receptive is not well understood. Our recent research has identified that proprotein convertase 6 (PC6), an important master switch responsible for activating other proteins, is tightly regulated in the uterus during its preparation for receptivity and critical for implantation. This project will examine how PC6 acts in the human uterus to make it receptive, by identifying the factors that PC6 controls and how this controlling works. We will use a cell culture model with cells isolated from human term placenta. In addition, there is no means of readily testing whether the uterus is receptive owing to the lack of reliable biomarkers. In this study we will determine whether PC6 (and those molecules controlled by PC6) are potential biomarkers for uterine receptivity. This will be achieved by examining uterine biopsies and uterine washings collected from proven fertile volunteers and patients of proven endometrial infertility. This study will greatly enhance our understanding of how a critical molecule, PC6, acts in the uterus for implantation. The results will provide new knowledge regarding uterine preparation for implantation. The study has considerable implication for developing much-needed diagnostic and therapeutic tools for uterine receptivity and infertility.Read moreRead less
Critical Role Of Proprotein Convertase 6 In Human Uterine Epithelium For Embryo Implantation And Clinical Implications
Funder
National Health and Medical Research Council
Funding Amount
$643,899.00
Summary
Implantation of an embryo into the uterus is a key step for human development. Implantation failure causes embryonic death, pregnancy loss and infertility. Conversely, preventing implantation is an attractive approach for contraception. We have established that proprotein convertase 6 (PC6) is a master regulator of implantation. We will investigate how PC6 works in a woman's uterus, and how we can use this knowledge to improve implantation in IVF and to develop PC6 drugs for new contraceptives.