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.
I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
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.
Toll-like Receptor And MyD88 Signalling In The Testis
Funder
National Health and Medical Research Council
Funding Amount
$498,411.00
Summary
Infertility affects one in seven couples desiring children. A proportion (5-10%) of the male partners in these couples have immunological reactions against their own sperm. The testes, where sperm are made, and the immune system normally exist in a balanced, beneficial relationship, but sometimes this relationship goes wrong. This can also lead to chronic pain and increased risk of testicular cancer. The project investigates this relationship in order to provide assistance for these men and thei ....Infertility affects one in seven couples desiring children. A proportion (5-10%) of the male partners in these couples have immunological reactions against their own sperm. The testes, where sperm are made, and the immune system normally exist in a balanced, beneficial relationship, but sometimes this relationship goes wrong. This can also lead to chronic pain and increased risk of testicular cancer. The project investigates this relationship in order to provide assistance for these men and their partners.Read moreRead less
This project aims to study the hormonal control of Sertoli cell development and function. In the testis, these highly specialised cells provide essential nutritional and structural support for sperm production. In current NHMRC-supported research we created a unique mouse model to study the individual roles of two key reproductive hormones FSH and testosterone in spermatogenesis. This novel approach involved the selective expression of transgenic FSH on the hormone-deficient background of hpg mi ....This project aims to study the hormonal control of Sertoli cell development and function. In the testis, these highly specialised cells provide essential nutritional and structural support for sperm production. In current NHMRC-supported research we created a unique mouse model to study the individual roles of two key reproductive hormones FSH and testosterone in spermatogenesis. This novel approach involved the selective expression of transgenic FSH on the hormone-deficient background of hpg mice, which normally lack both androgens and FSH. Our analysis revealed that FSH provided the main stimulation for Sertoli cell and early germ cell proliferation, whereas FSH required testosterone for later stages of sperm formation. In this proposal we now plan to investigate FSH and the changing steroidal contributions during the critical postnatal stage of Sertoli cell development. We will study individual of combined actions of FSH and steroids, including the controversial role of estradiol in Sertoli and germ cell function, which may all have profound consequences on sperm production and male fertility. We will also establish unique mouse models to address fundamental questions about the mechanisms of androgen actions in the testis, and the requirement for androgen receptor expression in Sertoli and neighbouring peritubular cells for the overall testosterone response. Furthermore, we will use new microarray gene screening technology to identify the FSH- and androgen-regulated gene pathways during Sertoli cell proliferation. This research has relevance to the controversial view of environmental steroids affecting human testicular development and reducing sperm counts, and offers the potential to uncover new causes of previously unexplained male infertility or testicular cancers, and to help develop better strategies for hormonal male contraceptives, and treatments for male infertitliy or cancer.Read moreRead less
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.
The Role Of MiRNAs In The Regulation Of Sperm Maturation
Funder
National Health and Medical Research Council
Funding Amount
$396,157.00
Summary
Male infertility is an extremely common condition affecting 1 in 20 Australian men. One of the major reasons for this pathology is that the spermatozoa have lost their ability to recognize the egg, a function that is acquired during epididymal maturation. In this project we shall investigate the regulation of epididymal sperm maturation and thus provide new and powerful insights into the causes of male infertility, with practical implications for diagnosis and treatment of this condition.
Approximately 1 in 25 men in the western world are infertile, and while environmental and genetic factors are recognized to contribute to disease, there is currently a poor understanding of the basic mechanisms regulating male fertility. Our long term goal is to identify and study key molecules involved in sperm production. Understanding the role of these molecules will provide insight into the causes of male infertility. Ultimately, these studies will assist to develop new treatments for male r ....Approximately 1 in 25 men in the western world are infertile, and while environmental and genetic factors are recognized to contribute to disease, there is currently a poor understanding of the basic mechanisms regulating male fertility. Our long term goal is to identify and study key molecules involved in sperm production. Understanding the role of these molecules will provide insight into the causes of male infertility. Ultimately, these studies will assist to develop new treatments for male reproductive disorders. Conversely, there is a huge need for additional male based contraceptives. Increased understanding of male fertility and identification of proteins exclusively involved in sperm production provides the opportunity to develop new contraceptive treatments.Read moreRead less
Persistent Chlyamdial Infection In The Testes : Development Of A Successful Vaccine Strategy For Males
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Males are a reservoir of infection and novel vaccine approaches to control Chlamydia infections in young men are needed urgently. This study will be essential for the development of interventions to control infection and will inform strategies for manipulating the immune system within the male reproductive tract that may be applied to other sexually transmitted pathogens. The studies will benefit the health and welfare of the Australian people under National Research Priority 2, promoting and ma ....Males are a reservoir of infection and novel vaccine approaches to control Chlamydia infections in young men are needed urgently. This study will be essential for the development of interventions to control infection and will inform strategies for manipulating the immune system within the male reproductive tract that may be applied to other sexually transmitted pathogens. The studies will benefit the health and welfare of the Australian people under National Research Priority 2, promoting and maintaining good health and a healthy start to life.Read moreRead less