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
Isolation And Function Of Human Oogenesis Genes Regulating Meiosis, Recruitment, Growth And Maturation Of The Oocyte.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes ....Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes that form the follicles containing the developing germ cells and the matured oocytes needed for IVF. The cohort of oocytes that can be harvested from any patient depends on unknown recruitment processes initiating development of a subset of the quiescent germ cells and happens in an unregulated and spontaneous manner. The present project will identify the known and unknown genes involved in recruitment of oocytes from the basal primordial population. These genes will become candidates for aiding infertile women, improving their response to fertility drugs, the development of novel contraceptive methods and potentially increasing the reproductive life span of women. Knowledge of the genes expressed in oocytes matured in vivo and in vitro will have an important bearing on the long-term opportunity to use fertility drugs in vitro instead of administration to patients for IVF. This would dramatically reduce the cost of IVF and the side-effects of hyperstimulation of ovaries of patients and the associated sequelae. The research project is a discovery program leading to the identification of the genes that govern oogenesis in the human. It is only recently that techniques have been developed to sufficient sensitivity to detect the small quantities of RNA proceeded by active genes in the individual germ cells and oocytes.Read moreRead less