I am a reproductive physiologist investigating the nature and actions of hormones, particularly steroids and transforming growth factor-? superfamily members, regulating follicle growth and oocyte quality in the ovary, implantation and breakthrough bleedi
Manipulating Ovarian Follicle - Oocyte Communication To Control Reproductive Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$567,424.00
Summary
Ovarian follicles provide the environment supporting oocyte (egg) development. Communication between cells of the follicle and oocytes modulate this environment. We discovered new cell surface molecules that receive the signals from the oocyte and we identified a class of drug compounds that can modulate this signalling. This discovery offers a unique potential to therapeutically intervene in this signalling process and both improve infertility therapies and develop new non-steroidal contracepti ....Ovarian follicles provide the environment supporting oocyte (egg) development. Communication between cells of the follicle and oocytes modulate this environment. We discovered new cell surface molecules that receive the signals from the oocyte and we identified a class of drug compounds that can modulate this signalling. This discovery offers a unique potential to therapeutically intervene in this signalling process and both improve infertility therapies and develop new non-steroidal contraceptives.Read moreRead less
Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and and ....Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and androgen will disrupt ExG development.Read moreRead less
Modulation Of MicroRNA Activity In The Testis: A New Paradigm For Male Fertility?
Funder
National Health and Medical Research Council
Funding Amount
$419,170.00
Summary
Sperm production in the testis is driven by the reproductive hormones, follicle-stimulating hormone (FSH) and testosterone. In this grant, we will investigate how a new class of molecules, called microRNAs, act to transmit the signals from FSH and testosterone to the cellular machinery of the testis, particularly at junctions between cells. This information has the potential to impact on our understanding of the causes of male infertility.
Obesity And Infertility: Effects Of Diet-induced Insulin Resistance On Oocyte Quality.
Funder
National Health and Medical Research Council
Funding Amount
$533,510.00
Summary
The health of an embryo (and subsequently child) is largely determined by the health of the mother. It is well documented that women who have poor pre-pregnancy health due to obesity are more likely to have difficulty conceiving due to irregular ovulations and early embryo loss. My research using obese mice has found that these fertility problems are partly due to alterations in the oocytes (eggs) within the ovary. Its surrounding cells and fluid provide the oocyte with all of its required nutri ....The health of an embryo (and subsequently child) is largely determined by the health of the mother. It is well documented that women who have poor pre-pregnancy health due to obesity are more likely to have difficulty conceiving due to irregular ovulations and early embryo loss. My research using obese mice has found that these fertility problems are partly due to alterations in the oocytes (eggs) within the ovary. Its surrounding cells and fluid provide the oocyte with all of its required nutrients. I hypothesize that this follicular environment is altered in females that are obese leading to inappropriate nutritional signals and suboptimal development of the oocyte. The goals of my research are to use obese mice to 1) pinpoint exactly which metabolic alterations lead to decreased oocyte development; 2) determine how these metabolic alterations change the oocyte and the cells surrounding it; 3) use the information gained to analyse ovarian cells of women and see if these same alterations occur in women who are obese. The findings will be highly significant because they will 1) provide a greater understanding of how the maternal environment communicates nutritional information to the oocyte, which ultimately forms the developing embryo. 2) expand our knowledge of the optimal nutritional conditions for oocyte and early embryo development. 3) identify biological mechanisms that are altered during obesity and lead to decreased female fertility. 4) aid in the development of improved agents for use at fertility clinics, for instance the development of solutions most closely mimicking the critical components of the normal ovarian environment, for use in the culture of oocytes and embryos. 5) provide a strong public health message to women of reproductive age: to achieve and maintain a healthy body weight prior to becoming pregnant.Read moreRead less
Insulin Resistance In Polycystic Ovary Syndrome And The Role Of Skeletal Muscle And Adipose Tissue
Funder
National Health and Medical Research Council
Funding Amount
$416,115.00
Summary
11% of women have polycystic ovarian syndrome(PCOS), characterised by insulin resistance, irregular periods and infertility. These women are prone to obesity, diabetes and potentially, heart disease. Treatments include lifestyle modifications +-- medical therapy. Lifestyle is first line, yet the best diet-exercise prescription is unclear. This study will provide insights into the cause of PCOS, will inform on the role of exercise in therapy and may identify targets for future therapies.
Kisspeptin And Its Receptor Mastermind Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Reproduction is controlled by the brain and gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. Finding critical regulators of GnRH has remained the most important goal for reproductive endocrinologists for over 30 years. The brain peptide hormone called kisspeptin and its receptor Kiss1R appear vital in the control of reproduction. This project will detail the role kisspeptin and Kiss1R play in controlling hormones from the brain that govern puberty and reproduction.
Why We Have Two Estrogen Receptors: The Role Of ERbeta In Folliculogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$576,053.00
Summary
The female hormone estrogen acts via receptors ERalpha and ERbeta. Little is known about the genes and proteins regulated by ERbeta. Ovarian granulosa cells and granulosa cell tumours express ERbeta. By studying the biology of normal and malignant granulosa cells we hope to understand the role that ERbeta plays in granulosa cells. These studies will identify areas for the development of new therapeutics or treatment strategies for a range of female-specific conditions including ovarian cancer.
Follicle-stimulating hormone (FSH) is vital for egg development, female fertility and health, and is widely used in assisted reproduction technology. But high levels of FSH are associated with premature infertility and menopause, and may lead to diseases like ovarian cancer. Understanding the biological pathways activated by elevated FSH may lead to new treatments for infertility and ovarian diseases (eg. cancer), as well as advancing new strategies for contraception.