Endometrial Receptivity For Embryo Implantation: Proprotein Convertase 6 And Plasma Membrane Remodeling
Funder
National Health and Medical Research Council
Funding Amount
$631,344.00
Summary
Implantation of an embryo into the uterus is a key step in establishing pregnancy; it requires a receptive uterus (fertile soil) and a healthy embryo (seed). Implantation failure causes pregnancy loss and infertility, and is also a major limiting factor in IVF. We have established that proprotein convertase 6 (PC6) is a master regulator of uterine receptivity for implantation. We will investigate how PC6 works in a woman’s uterus, and how we can use this knowledge to improve implantation in IVF.
Leucine-rich Guanylate Kinase Is A Regulator Of Sperm Tail Development And Motile Cilia Function
Funder
National Health and Medical Research Council
Funding Amount
$540,191.00
Summary
In this grant we will define the function of an uncharacterized protein, LRGUK, in fertility and hydrocephalus (water on the brain). LRGUK has a critical role in sperm development. We will define the cell biology and biochemistry of LRGUK function, we will assess the incidence of LRGUK mutations in human fertility and explore LRGUK function in the brain. Data obtained will have relevance to the 1 in 20 young men who suffer from infertility and the 3 in 1000 children who develop hydrocephalus.
Katanin P80 Is A Key Regulator Of Microtubule Dynamics And Male Fertility.
Funder
National Health and Medical Research Council
Funding Amount
$603,756.00
Summary
Male fertility is a complex process requiring the co-ordinated activation of thousands of gene products. It is not surprising therefore that 1 in 15 Australian men are infertile. This project will explore an essential pathways for sperm production, specifically related to sperm shaping and motility. This work may ultimately have implications for the diagnosis and treatment of male infertility, but also for pathology in tissues will similar cellular structures.
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.
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.
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.
Life-saving chemo/radio-therapy commonly renders women and girls who survivor cancer infertile or sterile. We have discovered a new means of preserving the fertility of female mice exposed to chemo/radio therapy. In this project we will apply these advances to human ovarian tissue/eggs for the first time. We have access to these rare tissues for research purposes. This project will develop new approaches to fertility preservation for cancer survivors.
Finding The Missing Katanin Required For Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$417,214.00
Summary
Microtubules are a key element of all cells, including in the male germ line. In this project we will define the function of the microtubule severing protein KATNA1 in male fertility. This will be achieved using a unique model and state-of-the-art technologies. This project will have immediate relevance to the 1 in 20 Australian men who suffer from infertility but will also inform KATNA1 function in the many other tissues where KATNA1 is produced.
Activin And Androgen Crosstalk During Testis Development Programs Adult Fertility
Funder
National Health and Medical Research Council
Funding Amount
$700,740.00
Summary
Fertility in men is determined by how the testis grows during fetal and juvenile life. We recently discovered that the Sertoli cells which nurse developing sperm are highly sensitive to cross-talk between testosterone and the growth factor activin during puberty. This project studies how this cross-talk is controlled to understand how altered hormone actions in boys, including exposure to harmful endocrine disrupting chemicals, reduces adult fertility.
Therapeutic Potential Of Transforming Growth Factor-beta Proteins For The Diagnosis And Treatment Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$942,961.00
Summary
We discovered and manufactured a growth factor produced uniquely by the egg. We named this growth factor cumulin. It is a powerful regulator of ovarian function and egg quality. This project will study the basic mechanisms of how cumulin works in the ovary. We will then develop an assay to measure it as a biomarker of human egg quality and quantity. New approaches in fertility preservation for cancer survivors will be developed using cumulin.