Differentiation Of Murine Embryonic Stem Cells To The Female Germ Line
Funder
National Health and Medical Research Council
Funding Amount
$57,342.00
Summary
In this project we aim to establish techniques to obtain viable and developmentally competent eggs from embryonic stem (ES) cells for studies on the molecular and cellular mechanisms of sex cell production. We expect to achieve ES cell derived eggs with similar fertilization and developmental potential as eggs developed naturally. Sterility resulting from cancer treatments and from genetic and non-genetic malformations can benefit from this ES cell therapy.
The normal processes of development of the embryo require that the information encoded in chromosomes be reprogrammed soon after fertilization. This process is rather fragile and disturbance of the early embryo can upset it. Recent studies for the chief investigator's provide new understanding of the normal processes of reprogramming. The project will explore and validate the implications of these new discoveries and provide a basis for future alleviation of abnormalities to development.
I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
Male Infertility And Defective Sperm-oocyte Interaction
Funder
National Health and Medical Research Council
Funding Amount
$244,614.00
Summary
Infertility affects 15% of people and although not usually ill, they are extremely distressed by the condition. In vitro fertilisation (IVF) with normal sperm and intracytoplasmic sperm injection for sperm defects, can assist such patients have a family, but these treatments are expensive and not always successful. The causes of male infertility are largely unknown, diagnostic methods are crude and there is usually no treatment to promote natural conception. Conventional semen analysis provides ....Infertility affects 15% of people and although not usually ill, they are extremely distressed by the condition. In vitro fertilisation (IVF) with normal sperm and intracytoplasmic sperm injection for sperm defects, can assist such patients have a family, but these treatments are expensive and not always successful. The causes of male infertility are largely unknown, diagnostic methods are crude and there is usually no treatment to promote natural conception. Conventional semen analysis provides limited information on fertilising ability. Our work over 15 years has shown that many patients go undiagnosed, particularly those with defects impairing fertilisation. During human fertilisation, sperm bind to the zona pellucida, a coat around the egg, via the membrane over a cap like structure on the sperm head called the acrosome. Binding of a sperm triggers the acrosome reaction, the process by which the membranes covering the acrosome fuse and the acrosomal contents are released. The sperm then penetrates the zona pellucida, binds to the membrane of the egg and is taken into the cytoplasm. We have developed tests to assess sperm binding to the zona pellucida and the acrosome reaction using eggs that failed to fertilise during clinical IVF. These tests show defects of sperm binding to the zona pellucida and the zona pellucida induced acrosome reaction are present in over 25% of patients without other obvious causes for their infertility. The men are severely infertile but have normal sperm by conventional tests. In this project we will determine if there are changes in membrane proteins in sperm which do not bind to the zona pellucida or undergo the acrosome reaction. We will categorise patients on the responses of their sperm to activation of key enzymes and other regulatory molecules involved in the fertilisation process. This will allow us to select subjects for further examination of protein abnormalities and genetic causes of the conditions.Read moreRead less
We propose to determine if a recently discovered biological mechanism plays crucial roles in the development of eggs and sperm. To achieve this, we will remove or mutate this pathway specifically in developing eggs and sperm , then examine the effect. Preliminary results indicate that the mechanism does play important roles mutated eggs fail to complete maturation. These studies will tell us more about what makes a healthy egg and sperm, and are relevant to female and male fertility.
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.
Metabolic And Molecular Basis Of Embryo Signalling
Funder
National Health and Medical Research Council
Funding Amount
$409,836.00
Summary
Cells in the body are powered by mitochondria that essentially generate the energy required for development. This grant will determine how the environment affects the mitochondria in the developing embryo and determine the impacts to the embryo and pregnancy if a mitochondria is partially shut down.
It is clear that the health and disease burden of offspring can be programmed by events before birth. This project will answer questions as to how this programming occurs. My focus is to understand how the environment affects the oocyte, sperm and embryo and how this impacts on the offspring. We will specifically study the effects of obesity and nutritional status of the parents but also the in vitro environment with a view to improving IVF outcomes.
Molecular Basis For Female Age-associated Decline In Oocyte Quality And Fertility
Funder
National Health and Medical Research Council
Funding Amount
$71,792.00
Summary
Many women cannot have children because of suboptimal egg quality, often due to ageing. In order for novel strategies to be developed for improving egg quality, it will first be important to understand how key factors in eggs are regulated. This project will use state-of-the-art techniques to interrogate a pivotal pathway we have discovered in eggs that could be responsible for age-related decline and could hold the key to new approaches for rejuvenating eggs.
Exploitation Of Unique Growth Factors To Develop New Products For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$132,525.00
Summary
Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro ma ....Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro maturation (IVM), which drastically reduces the use-cost of drugs and the stress to patients. However, oocyte IVM has been slow to live up to its potential and the technology is still not in widespread clinical practice, mainly due to disappointing success rates in women. We have been studying oocyte IVM in animals for many years, and have recently made a significant technological breakthrough, improving success rates by ~50%. In this field, a 50% increase in efficiency is substantial and has significant clinical and commercial application. Currently, we are the only group worldwide with this technology. Over the course of this 2-year project we will conduct follow-up experiments to refine this discovery and investigate the feasibility of using this approach to treat human infertility. We are already in negotiations with two medical device manufacturers to licence this technology. We expect that this project will lead to a series of products and technologies that will enter a clinical trial for the treatment of infertility within 2-3 years.Read moreRead less