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.
Izumo1 And Its Role In Male Infertility And Male Contraception
Funder
National Health and Medical Research Council
Funding Amount
$317,371.00
Summary
The project will study the role of the essential sperm-egg fusion protein Izumo1. Without some infertile men, this protein fails to move to the correct location in spermatozoa.
Cysteine-rich Secretory Protein Regulation Of Ion Channels In Male Fertility And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$474,309.00
Summary
Diagnosis of the precise causes of male infertility and the development of male contraceptives requires improved understanding of sperm function. The Cysteine-Rich Secretory Proteins (CRISPs) are produced in the male reproductive tract where they regulate sperm function. Our project will demonstrate the essential requirement for CRISPs in sperm function and investigate their role in other tissues of the reproductive tract, including the prostate where they may be involved in prostate cancer.
Understanding The Molecular Basis Of Epididymal Maturation: How Does The Epididymis Modify Spermatozoa, Allowing Them To Recognise The Egg ?
Funder
National Health and Medical Research Council
Funding Amount
$585,898.00
Summary
Male infertility is a significant clinical problem affecting one in twenty Australian men. A common feature of this condition is the sperm’s inability to recognize the egg. Sperm gain this property as they transit an organ known as the epididymis. We have produced genetically modified mice with a specific epididymal defect that prevents sperm-egg recognition. This study will examine the structure of these defective sperm to generate new insights into the molecular basis of sperm-egg interaction.
Understanding Sperm Motility For Infertility And Contraceptive Purposes
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
Male infertility is a significant clinical problem affecting one in twenty Australian men. The most common feature associated with this condition is defects in sperm motility. Regulation of sperm motility occurs through the epididymis and upon ejaculation. This study will examine how two kinases, essential for flagella bending, regulate sperm motility. Through the tools developed, we will investigate further defectives in infertile individuals with impaired sperm motility.
Novel Analogues Of Human INSL3 As Antagonists And Probes Of Testicular Function
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
The hormone, insulin-like peptide 3, has recently been shown to act directly on male and female germ cells to cause their maturation. It has considerable promise as a therapeutic agent for the regulation of fertility. Drugs based on the peptide may be used to assist in cases of infertility, and drugs that block its action have great potential as male and female contraceptives. Towards these goals, our project aims to understand how this peptide exerts its unique biological effects.
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
This project aims to study how the two main hormones, FSH and testosterone, control the development and production of sperm throughout adult life. In previous NHMRC-supported research we were the first to overturn the long-standing belief that FSH was vital to the start of sperm production in all warm-blooded animals. This insight was achieved from experiments using a genetically modified strain of mouse. We used this mouse strain to develop a new experimental paradigm to provide unique insight ....This project aims to study how the two main hormones, FSH and testosterone, control the development and production of sperm throughout adult life. In previous NHMRC-supported research we were the first to overturn the long-standing belief that FSH was vital to the start of sperm production in all warm-blooded animals. This insight was achieved from experiments using a genetically modified strain of mouse. We used this mouse strain to develop a new experimental paradigm to provide unique insight into how hormones start up and support sperm production. In this present proposal we wish to take this research further. Although we have shown that FSH is not vital to the startup or continuing of sperm production, we believe it still does have an important role in causing the growth of a large enough population of Sertoli cells of the testis. These highly specialised cells have the unique job to support, nourish and coordinate the production of sperm. Sertoli cells are known to be the only target in the body for FSH and so that FSH must act upon them exclusively. We believe this occurs almost solely during early life - starting before birth and into early infancy - well before adult life when sperm are produced for the first time. In this way these processes being studied determine the size of mature testis. Our new approaches to studying the question of how the two main hormones control sperm production involve developing new types of genetically modified mice which have extra and exclusive FSH activity as well as some new research methods to be applied to understanding how FSH acts on the Sertoli cell using techniques derived from gene therapy and from cell transplantation. This research has the possibility to uncover new causes of previously unexplained male infertility (the majority having no known cause so far), to help develop better hormonal male contraceptives, and to quetion the need for expensive treatments for some infertile men.Read moreRead less
Mechanisms Of Negative Feedback Regulation Of GnRH By Testosterone In Males
Funder
National Health and Medical Research Council
Funding Amount
$243,336.00
Summary
This project will improve our knowledge of the hormonal control of reproduction in males. The hormone testosterone, produced by the testes, acts on the brain to control the secretion of a substance called gonadotrophin releasing hormone (GnRH). GnRH acts on a small gland at the base of the brain to cause the production of hormones called gonadotrophins, that are essential for reproduction. These gonadotrophins act on the testes to ensure the production of sperm and other hormones, including test ....This project will improve our knowledge of the hormonal control of reproduction in males. The hormone testosterone, produced by the testes, acts on the brain to control the secretion of a substance called gonadotrophin releasing hormone (GnRH). GnRH acts on a small gland at the base of the brain to cause the production of hormones called gonadotrophins, that are essential for reproduction. These gonadotrophins act on the testes to ensure the production of sperm and other hormones, including testosterone. We plan to determine how testosterone acts on the brain to control GnRH secretion. To do this we will use male sheep and conduct a series of experiments designed to show where in the brain testosterone acts to ultimately affect the nerve cells that produce GnRH. Testosterone and similar compounds are increasingly being used as treatments for infertility, as a male contraception and misused as anabolic steroids. A thorough knowledge of how testosterone acts in the brain is necessary to improve treatments for reproductive disorders and ultimately to improve reproductive health in men.Read moreRead less