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.
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
The Characterisation Of An Essential Regulator Of Pre-mRNA Splicing Required For Germ Cell Function And Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$1,116,739.00
Summary
The male germ line is a fantastic system within which to define processes of fundamental importance to cell biology and health broadly. Within this grant we will define the role of a poorly described RNA splicing factor in all of stem cell function (spermatogonia), meiosis (spermatocytes) and in the remarkable metamorphosis underlying spermatid maturation. This will be done using a range of phenotypic characterizations, CHIP and RNA Seq technologies and gene sequencing.
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.
The Mechanism Of Spermatid Differentiation - A Link To Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$506,425.00
Summary
To discover novel regulators of male fertility, we have screened libraries of mutant mice generated by a chemical mutagen. This project aims to define the function of the mutated gene identified in a male-specific infertile mutant mouse line. The mutated gene has been proposed to play a role in regulating cell death and suppress lung tumour formation. Our data may reveal novel options for male infertility treatment and for the development of male contraception and lung cancer biomarkers.
Male fertility requires sufficient production of healthy sperm in the testis. This project builds on our discovery that testicular cells communicate via the wnt family of proteins during sperm development, and that interruption of their activities reduces fertility in mice. We propose to use mouse models to study the precise steps in sperm production affected by Wnt signalling and how it works.
RNA Binding Protein Musashi: Role In Folliculogenesis And Oocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Women in Australian have opted for social and economic reasons to delay both marriage and childbirth. Both infertility and congenital abnormality is associated with advancing maternal age as the ovarian pool of oocytes declines in number and quality. In this project we aim to gain an understanding of the molecular mechanisms underpinning healthy oocyte development. Insights gained have the potential to alleviate miscarriage, infertility and congenital abnormalities in Australian families.
Characterisation Of Cumulus Cell Molecular Mediators Of Oocyte Health
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Many women are poorly fertile because of poor egg quality due to age, disease and lifestyle. IVF can assist, but requires large doses of hormone, which can lead to significant health risks. IVM is an alternative lab technique to IVF, but has very poor success. We discovered that synthetic proteins copied from recently discovered egg proteins can be added to the egg and substantially increase IVM success. Answering why will further will aid treatment for infertile women
We propose to determine if a recently discovered biological mechanism plays crucial roles in the development of eggs and sperm. To achieve this, we will remove or mutate this pathway specifically in developing eggs and sperm , then examine the effect. Preliminary results indicate that the mechanism does play important roles mutated eggs fail to complete maturation. These studies will tell us more about what makes a healthy egg and sperm, and are relevant to female and male fertility.