Women are born with a limited supply of eggs and are unable to make new eggs after birth. Because of this, the number and health of eggs established within the ovary early in life influence the length of time for which a female will be fertile, her age at menopause, and the health of her offspring. This project aims to shed some light on the mechanisms that control egg supply and reproductive longevity in women by investigating the role of the cell death protein Bid within the ovary.
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
Manipulating Ovarian Follicle - Oocyte Communication To Control Reproductive Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$567,424.00
Summary
Ovarian follicles provide the environment supporting oocyte (egg) development. Communication between cells of the follicle and oocytes modulate this environment. We discovered new cell surface molecules that receive the signals from the oocyte and we identified a class of drug compounds that can modulate this signalling. This discovery offers a unique potential to therapeutically intervene in this signalling process and both improve infertility therapies and develop new non-steroidal contracepti ....Ovarian follicles provide the environment supporting oocyte (egg) development. Communication between cells of the follicle and oocytes modulate this environment. We discovered new cell surface molecules that receive the signals from the oocyte and we identified a class of drug compounds that can modulate this signalling. This discovery offers a unique potential to therapeutically intervene in this signalling process and both improve infertility therapies and develop new non-steroidal contraceptives.Read moreRead less
Polycystic ovary syndrome (PCOS) affects 5-10% of women worldwide, yet its origins remain unknown. Androgens are implicated in the development of PCOS, but the decisive, invasive studies needed to confirm and elucidate their roles are not feasible in women. Hence, using our innovative mouse models of androgen resistant female mice, this study will determine the role of androgens in PCOS aiming to better understand, and identify new treatments for this common female reproductive disorder.
Reappraisal Of The Mechanisms Underlying Implantation Success Or Failure
Funder
National Health and Medical Research Council
Funding Amount
$750,755.00
Summary
Infertility affects 1:6 Australian couples; these seek help. However, for each IVF cycle, there is only ~18.5% chance of a live birth, significantly due to failure of embryo implantation. We discovered nano-vesicles in the uterine cavity, that are released from the womb lining and taken up by the pre-implantation embryo to improve its implantation potential. We will determine how this extracellular environment can enhance implantation success and circumvent/management of infertility.
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.
Re-energising The Preimplantation Embryo To Extend Lifetime Health
Funder
National Health and Medical Research Council
Funding Amount
$1,156,936.00
Summary
Diseases of aging are associated with shortening at the ends of chromosomes called telomeres. The length of an individual’s telomeres is established during embryo development, and in situations where embryo development is compromised such as with maternal obesity the normal process of telomere lengthening may not occur. We will determine how such disruptions in embryo telomere lengthening contribute to poor health in adulthood and test ways to restore the natural process.
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.
Role Of Snail Family Proteins In Male Fertility And Testicular Cancer
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Male fertility requires production of healthy sperm in the testis. This project builds on our discoveries that testicular cells regulate gene activity via the Snail family of proteins during sperm development, and that interruption of their activities reduces fertility in mice and fruitflies. Snail proteins are also active in cancer cells. We propose to study the precise steps in sperm production affected by Snail proteins and how they affect the progression of testicular cancer.
Inflammatory Cytokines As Causal Agents In Peri-conception Programming Of Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$604,046.00
Summary
Events at conception set the trajectory of fetal developmental that will determine health of children after birth and in later life. Susceptibility to obesity and metabolic conditions is established at this very early time. This project will define the molecular signals affecting the embryo in the event of maternal or paternal infection, diet and stress. The results will help us devise health advice for intending parents to improve child health and help prevent onset of metabolic disorders.