Role Of Liver Receptor Homologue-1 (LRH-1) In Male Germ Cells
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
Historically the steroid sex hormones - oestrogens and androgens - have been regarded as female- and male- specific sex hormones, respectively. Oestrogens are produced by the ovary and regulate female-specific processes such as ovulation and development of female sexual characteristics, whereas androgens are produced by the testis and regulate male-specific functions. However it is now clear that the distinction between oestrogen and androgen is not a sharp one. For example, we now know that oes ....Historically the steroid sex hormones - oestrogens and androgens - have been regarded as female- and male- specific sex hormones, respectively. Oestrogens are produced by the ovary and regulate female-specific processes such as ovulation and development of female sexual characteristics, whereas androgens are produced by the testis and regulate male-specific functions. However it is now clear that the distinction between oestrogen and androgen is not a sharp one. For example, we now know that oestrogens are produced within the testis and play a very important role in male fertility. Human males patients who are unable to synthesise oestrogens are infertile. Similarly, mice that cannot produce oestrogens are also infertile, due to a defect in sperm production. Oestrogens are therefore critical for normal male fertility, and reduced oestrogen production within the testis may be a significant cause of infertility which would be easily treatable in the clinic. The protein LRH-1 regulates oestrogen production in other tissues. This proposal aims to identify the role of LRH-1 in testicular oestrogen production by identifiying the genes regulated by LRH-1 and the proteins that interact with it in the testis. We also aim to study the structure of these proteins in infertile men. These studies will define new genes associated with male infertility and may lead to the development of more effective treatments for this common condition.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.
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
The Identification Of Male Meiosis Genes Using A New Mouse Line And Human Genome Scans For Gene Copy Number Variations
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Infertility affects 1 in 25 Australian men and meiosis is a key process in male fertility, yet we know very little about the mechanisms that control it. We will use a new point mutant mouse model of meisois failure to identify a novel regulator of male fertility. Further, we hypothesize that changes in gene copy number will lead to meiosis arrest and infertility in some men. Such variations will be assessed through a whole genome scan of a unique set of infertile men.
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