Modulation Of Telomere Length And Subtelomeric DNA Methylation In Response To Oxidative Stress In The Male Germ Line; Implications For Tumorigenesis In The Offspring
Funder
National Health and Medical Research Council
Funding Amount
$310,684.00
Summary
This research project is designed to elucidate how the quality of a father’s spermatozoa can impact upon the health and wellbeing of his children. We hypothesize that factors, such as infertility, heavy smoking or age create a state of oxidative stress in the testes and that this stress influences the genetic structure of spermatozoa in such a way that the incidence of spontaneous mutations and susceptibility-to-cancer are significantly elevated in the offspring.
Advancing maternal age is associated with the progressive loss of fertility, increased miscarriage and a greater risk of bearing children with birth defects. These adverse reproductive outcomes result, in part, from the loss of egg quality with age. We aim to identify and characterise genes involved in the age-related decline in egg quality. The long-term goal of this research is to develop novel strategies to improve fertility outcomes for women who chose to delay pregnancy until later in life.
A Novel Procedure For Efficacious Gonadotrophin-free Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
Infertility is common and is associated with health risks and is expensive. Using laboratory animals, we have developed a unique procedure, which has comparable success rates to IVF but crucially, it eliminates the need for ovarian hormone therapy used in IVF. A clinical trial using this method has started in Brussels and in this project we will examine cells from that trial and from animals to investigate the underlying mechanisms to enable safe and rapid clinical implementation.
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
One in five Australian couples experience infertility and poor egg quality is a major contributing factor. Developing eggs in the ovary are surrounded by helper cells and we have discovered a new form of communication between these cells and the egg that regulates egg quality. This project will investigate the details of this dialogue and how it improves egg quality. New knowledge gained from this project will improve our understanding and treatment of infertility and reproductive diseases.
Obesity And Infertility: Effects Of Diet-induced Insulin Resistance On Oocyte Quality.
Funder
National Health and Medical Research Council
Funding Amount
$533,510.00
Summary
The health of an embryo (and subsequently child) is largely determined by the health of the mother. It is well documented that women who have poor pre-pregnancy health due to obesity are more likely to have difficulty conceiving due to irregular ovulations and early embryo loss. My research using obese mice has found that these fertility problems are partly due to alterations in the oocytes (eggs) within the ovary. Its surrounding cells and fluid provide the oocyte with all of its required nutri ....The health of an embryo (and subsequently child) is largely determined by the health of the mother. It is well documented that women who have poor pre-pregnancy health due to obesity are more likely to have difficulty conceiving due to irregular ovulations and early embryo loss. My research using obese mice has found that these fertility problems are partly due to alterations in the oocytes (eggs) within the ovary. Its surrounding cells and fluid provide the oocyte with all of its required nutrients. I hypothesize that this follicular environment is altered in females that are obese leading to inappropriate nutritional signals and suboptimal development of the oocyte. The goals of my research are to use obese mice to 1) pinpoint exactly which metabolic alterations lead to decreased oocyte development; 2) determine how these metabolic alterations change the oocyte and the cells surrounding it; 3) use the information gained to analyse ovarian cells of women and see if these same alterations occur in women who are obese. The findings will be highly significant because they will 1) provide a greater understanding of how the maternal environment communicates nutritional information to the oocyte, which ultimately forms the developing embryo. 2) expand our knowledge of the optimal nutritional conditions for oocyte and early embryo development. 3) identify biological mechanisms that are altered during obesity and lead to decreased female fertility. 4) aid in the development of improved agents for use at fertility clinics, for instance the development of solutions most closely mimicking the critical components of the normal ovarian environment, for use in the culture of oocytes and embryos. 5) provide a strong public health message to women of reproductive age: to achieve and maintain a healthy body weight prior to becoming pregnant.Read moreRead less
Characterisation Of The Pathways Leading To DNA Demethylation In The Embryo.
Funder
National Health and Medical Research Council
Funding Amount
$634,573.00
Summary
Complex living creatures like humans have specialised cells that co-operate to form important organs like brains and reproductive organs. Specialised cells have specific genes locked on or off. When a sperm fertilises an egg, all the switches of the genes that are locked on or off get reset to neutral so that the fertilised egg can divide and grow into all cell types in the body. We do not know how this resetting happens in the egg. This project seeks to discover the mechanism involved.
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.
Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian c ....Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. An understanding of the way gene expression and hence tissue differentiation is altered after sex reversal will inform us about the causes and consequences of normal and abnormal sexual development, gonadal malignancies and infertility. The gonad is unusual in that two completely different organs can arise from an essentially identical primordium, so that errors in development lead to intersexual phenotypes. We will use our new experimental animal model to clarify these processes.Read moreRead less
Roles Of TGFbeta Receptor TGFBR3 (Betaglycan) In Testis Development
Funder
National Health and Medical Research Council
Funding Amount
$332,660.00
Summary
Diseases of the reproductive tract are major health issues. At lease 1 in 100 live births display some sort of gonadal defects. Later in adulthood, one in six couples are affected by infertility, and cancers of the reproductive tract which result in a significant number of deaths each year. This project focuses on understanding the role of the transformation growth factor beta receptor3 (Tgfbr3) in the embryonic and neonatal testis and its impact on adult male reproductive capacities and health.