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.
I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
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.
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.
Regulation Of Immune Responses In The Adult Testis And Male Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$637,857.00
Summary
This project investigates the main inflammatory cell, the macrophage, in male fertility and reproductive health. These studies investigate the macrophages found in the testes and the regulation of their functions required to protect and support the developing sperm. Understanding these processes will lead to new methods for treating male infertility, chronic pain and reproductive tract infections, as well as broader understanding of inflammatory disease, transplantation and autoimmunity.
The Negative Transgenerational Impacts Of Paternal Obesity Are Inherited Through Aberrant Methylation And MicroRNA Conetent Of Germ Cells.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
We have shown that obese fathers have reduced sperm function that negatively impacts upon their offspring’s health. But we do not understand the underlying alterations to sperm DNA that cause offspring to inherit poor health from an obese father, and whether these offspring also exhibit the same alterations. My project aims to identify alterations made to sperm DNA and RNA caused by obesity that are inherited by the next generation, ‘programming’ them for poor metabolic and reproductive health.
It has been recently found that some factors during intrauterine life are important and previously unsuspected determinants of cardiovascular disease decades later. The mechanisms are not yet clear but placental function in maintaining fetal nutrition and hormone secretion are likely to be important. Similar mechanisms have been found to affect female reproductive function and non-reproductive hormones in humans but the potential effects involving male reproductive health have not been studied s ....It has been recently found that some factors during intrauterine life are important and previously unsuspected determinants of cardiovascular disease decades later. The mechanisms are not yet clear but placental function in maintaining fetal nutrition and hormone secretion are likely to be important. Similar mechanisms have been found to affect female reproductive function and non-reproductive hormones in humans but the potential effects involving male reproductive health have not been studied so far. This project aims to search for prenatal factors that affect the development of the testis and prostate. By this means, prenatal factors may be an important in determining susceptibility to male infertility by lowering sperm output, androgen deficiency due to diminished testicular testosterone secretion and prostate disease notably prostatic hyperplasia. In this study we will employ our own specialised techniques for highly accurate measurement of the size of prostate zones and the testis using high frequency ultrasound. We will identify a birth cohort - a group of men born in a single hospital around 1970 - in whom we will measure prostate zones and testis size by ultrasound together with the hormonal markers relevant to the testis and prostate to examine whether any changes seen according to birthweight are due to concordant changes in hormones. This study could change the way in which disorders of male reproductive health are considered by focusing on factors occurring before and shortly after birth rather than on genetic or ambient environmntal factors in adult life which have been the overwhelming focus of research over recent decades.Read moreRead less
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