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.
Transplantation of frozen ovarian tissue is being used by young patients at risk of losing ovarian function. This study aims to maximize the likelihood that patients who have ovarian tissue collected, frozen and returned will acheive the desired outcome of returning ovarian hormonal cyclicity, ovulation, or fertility.
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.
Hospital Admission, Cerebral Palsy, Intellectual Disability And Birth Defects In Assisted Conception Infants.
Funder
National Health and Medical Research Council
Funding Amount
$115,110.00
Summary
We have recently completed a study examining the prevalence of birth defects in assisted conception infants born in Western Australia from 1993-1997. Contrary to reassuring claims by other researchers in this area, we found that assisted conception infants have a two-fold increased risk of being diagnosed with a major birth defect by one year of age. We now propose to examine other long-term health outcomes in these children. This study involves record linkage between the WA Reproductive Technol ....We have recently completed a study examining the prevalence of birth defects in assisted conception infants born in Western Australia from 1993-1997. Contrary to reassuring claims by other researchers in this area, we found that assisted conception infants have a two-fold increased risk of being diagnosed with a major birth defect by one year of age. We now propose to examine other long-term health outcomes in these children. This study involves record linkage between the WA Reproductive Technology Register and four other population-based databases. The prevalence of cerebral palsy, intellectual disability, hospital admission and birth defects in assisted conception children born in WA between 1993 and 2001 will be compared to that seen in all other Western Australian children born over the same time period. The collection of information on risks associated with assisted conception treatment is vital to allow adequate counselling of couples considering fertility treatment. Cerebral palsy, intellectual disability, birth defects and hospital admission are all serious adverse health outcomes and, despite the introduction of IVF to most Western countries twenty years ago, there are limited data in the literature concerning the occurrence of these conditions in assisted conception infants. Quantifying the contribution of assisted conception treatment to neonatal, infant and childhood morbidity and mortality is also important for the planning of health service provision. Although assisted conception births represent only a small proportion of total births in Australia, these infants may require a disproportionate level of health care services, such as neonatal intensive care treatment due to complications associated with preterm or multiple birth. The wide application of assisted conception treatment in Australia and the increased number of pregnancies achieved by these means reinforce the urgent need for valid data on the health of children born after these procedures.Read moreRead less