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.
The Role Of Transcription Factors In Regulating The First Round Of Gene Expression In The Early Embryo.
Funder
National Health and Medical Research Council
Funding Amount
$348,931.00
Summary
Assisted reproductive technologies result in a high incidence of multiple births. This is and adverse outcome that requires correction. It stems from the common transfer of several embryos due to the low chance of an individual embryo made by IVF resulting in a baby. This project will determine the normal pattern of gene expression in the embryo and define: (1) how it is adversely changed as a consequence of IVF; and (2) the extent that these changes are a cause of the low embryo viability.
Mechanisms Of P53 Induced Embryopathy After In Vitro Fertilisation.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
Assisted reproductive technologies (ART) cause many embryos not to survive to birth. We have shown that IVF causes increased expression of protein normally involved in stopping cells from dividing. This is a major cause of embryo death after IVF. This project will determine how this protein acts to cause embryonic death and assess strategies to prevent it.
A man's reproductive health and fertility is affected by processes that occur long before adulthood. The testis and sperm precursor cells first form in the fetus and then grow until the time of puberty, when the upper limit for sperm production is set. This project studies how one key signaling molecule, activin, helps establish normal testicular architecture and drives maturation of sperm precursor cells, and how it contributes to aberrent function in men with testicular cancer.
Positional Candidate Targets For Multiple Ovulation Genes
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
The frequency of non-identical twins is associated with fertility in individuals and populations, although we know little about mechanisms for twinning or effects on fertility. The likelihood for giving birth to non-identical twins is influenced by genetic factors. The probability of a subsequent twin pregnancy is increased fourfold in mothers of twins and roughly doubled for women whose mother or sister has had non-identical twins. Understanding why some women are more likely to have twins will ....The frequency of non-identical twins is associated with fertility in individuals and populations, although we know little about mechanisms for twinning or effects on fertility. The likelihood for giving birth to non-identical twins is influenced by genetic factors. The probability of a subsequent twin pregnancy is increased fourfold in mothers of twins and roughly doubled for women whose mother or sister has had non-identical twins. Understanding why some women are more likely to have twins will help us find key pathways that control normal ovarian function and important factors that influence success in assisted reproduction. The aim of this project is to search for these genes in families with two sisters who have given birth to non-identical twins. Previous studies have identified one strong target region and two possible regions containing genes for increased twinning. We now have additional families and will examine each region in more detail. We will also look for genes within each region that could be responsible for variation in twin frequency.Read moreRead less
Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulat ....Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulations over the first 5 days of mouse pregnancy on embryonic temporal and spatial organisation.Read moreRead less
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
Role Of Tumour Suppressor Genes In Early Embryopathy
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. The high mortality of the early embryo seems to be a general feature of ART but its causes and effectors are incompletely defined. It has been established that this high mortality is largely due to a marked retardation in ....Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. The high mortality of the early embryo seems to be a general feature of ART but its causes and effectors are incompletely defined. It has been established that this high mortality is largely due to a marked retardation in the rate of cell cycle progression by embryo cells, and commonly is associated with a form of cell 'suicide', known as apoptosis. In non-embryonic cells a group of genes known as the tumour suppressor genes (TSGs) are responsible for slowing cell-cycle progression and are commonly involved in inducing apoptosis following cell stress. The role of TSGs in the early embryo is not well studied. We have recently shown that the most important of the TSGs, P53, is normally kept at very low levels in the early embryo but that ART causes up-regulation of its expression. This upregulation is a major cause of the embryopathy associated with ART in an animal model but that genetic mutations that prevent P53 expression favours increased embryo development and viability. This project will examine whether ART also causes up-regulation other important TSGs and whether this occurs in human embryos. We will examine the hypothesis that ART increases the survival of embryos with mutations to the P53 gene (creating a postive genetic selection pressure in favour of these mutations); and which aspects of ART cause this positive selection. The project will demonstarte whether changes in the ART procedures have the potential to mitigate against selection of embryos bearing deletrious mutations.Read moreRead less
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