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
Androgen Receptor Activity In Normal And Abnormal Human Ovarian Function
Funder
National Health and Medical Research Council
Funding Amount
$416,696.00
Summary
Androgens are hormones normally associated with men, but women also produce androgens and they are essential for normal female health and reproduction. Imbalances in female androgen activity could account for approximately 50% of female infertility, but exactly how androgens behave in women is not well understood. Making too much androgen is the most common hormonal problem experienced by women in their reproductive years, and it affects the ovary in a way that can cause infertility. Women with ....Androgens are hormones normally associated with men, but women also produce androgens and they are essential for normal female health and reproduction. Imbalances in female androgen activity could account for approximately 50% of female infertility, but exactly how androgens behave in women is not well understood. Making too much androgen is the most common hormonal problem experienced by women in their reproductive years, and it affects the ovary in a way that can cause infertility. Women with this problem have polycystic ovary syndrome (PCOS). Gaining weight increases the chance of having problems with fertility and increases the risk of diabetes and heart problems in women with PCOS. The cause of PCOS is unknown, but it can occur in families, which indicates that some genetic factor is involved. On the other hand, the concept that some women do not produce enough androgen is only beginning to emerge and remains a controversial topic among medical experts. Part of the problem with this notion is that normal female androgen levels are very difficult to measure accurately, so no one can say for certain how much is too little. A recent scientific study in female mice indicates that poor androgen action causes infertility early in life because the ovary is ageing too quickly. A similar thing could possibly occur in women, but this has never been scientifically explored. However, we have some early evidence that shows abnormally low androgen levels in infertile women with signs of early aging in the ovary. Our study aims to understand the role that androgens play in normal and abnormal ovarian function. A large part of this study involves investigation of the androgen receptor, a molecule that controls what androgens can do inside body organs. We think that abnormal activity of this receptor will be involved in ovarian diseases that cause infertility in women. This understanding may lead to new means of diagnosing and treating infertility in women.Read moreRead less
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.
Polycystic ovary syndrome (PCOS) affects 5-10% of women worldwide, yet its origins remain unknown. Androgens are implicated in the development of PCOS, but the decisive, invasive studies needed to confirm and elucidate their roles are not feasible in women. Hence, using our innovative mouse models of androgen resistant female mice, this study will determine the role of androgens in PCOS aiming to better understand, and identify new treatments for this common female reproductive disorder.
Hormonal Control Of Serotli Cell Maturation And Function
Funder
National Health and Medical Research Council
Funding Amount
$512,898.00
Summary
This project will determine the key roles of androgen in the Sertoli cell, a unique highly specialised cell that provides essential nutritional and structural support for sperm production. Androgen acts via the androgen receptor (AR), which is vital for initiating and maintaining sperm development. In current NHMRC-funded research we successfully established new mouse models designed to study AR, in particular its regulation of gene expression, in the Sertoli cell. We revealed that genomic AR ac ....This project will determine the key roles of androgen in the Sertoli cell, a unique highly specialised cell that provides essential nutritional and structural support for sperm production. Androgen acts via the androgen receptor (AR), which is vital for initiating and maintaining sperm development. In current NHMRC-funded research we successfully established new mouse models designed to study AR, in particular its regulation of gene expression, in the Sertoli cell. We revealed that genomic AR activity within Sertoli cells is essential for 'induction' of complete sperm development. Ongoing work will develop unique 'inducible' transgenic models that will allow, for the first time, selective analysis of Sertoli AR in both 'developing' and 'adult' testes. Our innovative models will allow AR function to be switched on or off at any stage of development, providing unique opportunity to determine the key AR-regulated factors and pathways controlling induction, maintenance or restoration of sperm production. In past NHMRC research we created a novel transgenic model to study another major reproductive hormone, FSH. Using the hormone-deficient background of 'hpg' mice, we found that androgen and FSH act synergistically in the developing 'meiotic' germ cells that form sperm. Using the latest microarray gene technology we generated datasets of androgen-regulated genes with or without FSH activity, which combined with our unique transgenic AR and FSH models, will be used to identify key pathways, including those enhanced by androgen-FSH synergism, in the early testicular response. Our research will provide new knowledge of the precise roles and pathways of testicular AR actions, to ultimately identify key genetic and regulatory factors as targets for significantly improved therapy for male infertility, gonadal tumours, or contraception.Read moreRead less
This study is aiming to develop an unique mouse model in which to study the question whether testosterone plays an essential role in female reproductive and general health. It will develop a genetic mouse model for a biological state of complete resistance to the effects of androgens. Such mice and humans are well known among genetic males but this cannot occur naturally among genetic female mammals. By creating such a mouse line, this project will be able to test for the first time indetail whe ....This study is aiming to develop an unique mouse model in which to study the question whether testosterone plays an essential role in female reproductive and general health. It will develop a genetic mouse model for a biological state of complete resistance to the effects of androgens. Such mice and humans are well known among genetic males but this cannot occur naturally among genetic female mammals. By creating such a mouse line, this project will be able to test for the first time indetail whether testosterone has an impotant role in the development and function of the ovary and of other female tissues such as bone, muscle and the brain.Read moreRead less
Androgen Receptor Mechanims In Female Reproductive Physiology
Funder
National Health and Medical Research Council
Funding Amount
$539,773.00
Summary
Infertility occurs in one in six Australian couples with 50% attributable to females, thus, enhancing our understanding of ovarian and uterine function is of great importance. This project tests the proposal that androgens (steroid hormones) play a major role in regulating female reproductive physiology through their interaction with the androgen receptor. We have developed novel mouse models which we will use to determine the roles of androgens in regulating female reproductive function.