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.
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.
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
EGF Peptide Signalling Improves Oocyte Maturation And Quality
Funder
National Health and Medical Research Council
Funding Amount
$586,891.00
Summary
Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have developed significant new insights into mechanisms regulating egg quality. These insights have allowed us to develop a new approach to infertility treatment - crucially, one that eliminates the need for ovarian hormone therapy used in IVF. This project will investigate the basic mechanisms underlying our new approach to enable safe clinical ....Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have developed significant new insights into mechanisms regulating egg quality. These insights have allowed us to develop a new approach to infertility treatment - crucially, one that eliminates the need for ovarian hormone therapy used in IVF. This project will investigate the basic mechanisms underlying our new approach to enable safe clinical implementation.Read moreRead less
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.
Modulation Of MicroRNA Activity In The Testis: A New Paradigm For Male Fertility?
Funder
National Health and Medical Research Council
Funding Amount
$419,170.00
Summary
Sperm production in the testis is driven by the reproductive hormones, follicle-stimulating hormone (FSH) and testosterone. In this grant, we will investigate how a new class of molecules, called microRNAs, act to transmit the signals from FSH and testosterone to the cellular machinery of the testis, particularly at junctions between cells. This information has the potential to impact on our understanding of the causes of male infertility.
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.
Elucidating The Role Of Epididymosomes In The Transfer Of Fertility-modulating Proteins And Regulatory Classes Of RNA To Maturing Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$539,425.00
Summary
Sperm dysfunction represents a major underlying aetiology associated with male infertility. This proposal seeks to understand the mechanisms responsible for driving the functional maturation of spermatozoa and how these mechanisms are perturbed in response to environmental stressors.
The Importance Of The Blood-testis Barrier In Human Infertility
Funder
National Health and Medical Research Council
Funding Amount
$560,953.00
Summary
The blood-testis barrier (BTB) shields developing sperm from the circulation and immune system, which would see them as ‘foreign’. Loss of BTB function leads directly to infertility. Curiously, how the BTB ‘opens’ and ‘closes’ to allow entry without causing a ‘leak’ is unknown. We believe that activin A is the main gatekeeper, but this growth factor is also important in inflammation. Our goals are to show how activin A allows sperm cells entry, and how inflammatory diseases impact the BTB.
A BubR1-centred Network For Non-invasively Measuring Human Oocyte Quality
Funder
National Health and Medical Research Council
Funding Amount
$532,207.00
Summary
Oocyte quality is the most important determinant of pregnancy outcome. Selecting the best oocytes for fertility treatments like IVF would therefore greatly improve success rates and reduce costs. We have identified master oocyte regulators and have applied novel digital technology to measure these regulators in a single oocyte. This project will apply this expertise to develop new approaches for evaluating an oocyte’s potential thereby informing its suitability for use in fertility treatment.