Testis To Ovary: Hormonal Control Of Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$803,379.00
Summary
We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide f ....We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide formation of the ovary.Read moreRead less
The Early Life Origins Of Impaired Testicular Function: A Prospective Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$623,277.00
Summary
There is a widespread public perception that sperm counts are diminishing. This theory can only be tested by using a representative sample of young men, rather than biased populations (such as men presenting as sperm donors). We have the unique opportunity to test this theory, and to determine any early life events which may lead to reduced sperm counts, such as being growth restricted at birth, exposed to high levels of maternal oestrogens or smoking or being overweight in adolescence.
Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian c ....Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. An understanding of the way gene expression and hence tissue differentiation is altered after sex reversal will inform us about the causes and consequences of normal and abnormal sexual development, gonadal malignancies and infertility. The gonad is unusual in that two completely different organs can arise from an essentially identical primordium, so that errors in development lead to intersexual phenotypes. We will use our new experimental animal model to clarify these processes.Read moreRead less
Progesterone Receptor-mediated Coordination Of Oocyte-oviduct Communication During Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$86,128.00
Summary
Infertility affects 1 in 6 couples, often due to failed release of an egg from the ovary. The hormone progesterone is essential for this process. Our goal is to determine how progesterone signals the egg to ensure its correct release into the oviduct where fertilization may occur. To identify these signals, experiments will analyse ovary cells and eggs of mice, including mice that do not respond to progesterone. The results will provide much needed information about female reproductive health.
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