The Importance Of The Blood-testis Barrier In Human Infertility
Funder
National Health and Medical Research Council
Funding Amount
$560,953.00
Summary
The blood-testis barrier (BTB) shields developing sperm from the circulation and immune system, which would see them as ‘foreign’. Loss of BTB function leads directly to infertility. Curiously, how the BTB ‘opens’ and ‘closes’ to allow entry without causing a ‘leak’ is unknown. We believe that activin A is the main gatekeeper, but this growth factor is also important in inflammation. Our goals are to show how activin A allows sperm cells entry, and how inflammatory diseases impact the BTB.
P-glycoprotein: A New Player In The Placental Glucocorticoid Barrier
Funder
National Health and Medical Research Council
Funding Amount
$424,711.00
Summary
Adequate growth and development of the fetus are crucial for survival of the newborn. The placenta plays a central role in these processes, providing the fetus with appropriate nutrients and hormonal signals. The placenta also regulates the maternal-fetal passage of hormones, some of which have the capacity to limit fetal growth. These include glucocorticoid hormones from the mother's adrenal gland (eg cortisol) which are normally prevented from passing through the placenta to the fetus due to t ....Adequate growth and development of the fetus are crucial for survival of the newborn. The placenta plays a central role in these processes, providing the fetus with appropriate nutrients and hormonal signals. The placenta also regulates the maternal-fetal passage of hormones, some of which have the capacity to limit fetal growth. These include glucocorticoid hormones from the mother's adrenal gland (eg cortisol) which are normally prevented from passing through the placenta to the fetus due to the 'placental glucocorticoid barrier'. The primary focus of this proposal is the investigation of a potential new contributor to this barrier called P-glycoprotein (P-gp), recently shown to limit access of glucocorticoids to the brain. We propose that because the placenta expresses significant amounts of P-gp, it may help prevent maternal glucocorticoids from reaching the fetus and causing growth retardation. We will determine whether P-gp is a significant contributor to the placental glucocorticoid barrier, and measure how much P-gp is present in normal placentas throughout pregnancy. We will also assess whether there is less P-gp present in placentas of growth-retarded fetuses. Understanding how P-gp affects the passage of glucocorticoids across the placenta could help to treat certain cases of fetal growth retardation.Read moreRead less
The Role Of Oocyte-secreted Proteins In Primate Follicular Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$176,320.00
Summary
Mammalian eggs grow and develop in fluid filled sacks in the ovary called follicles. These structures nurture the egg for prolonged periods preparing it for ovulation and fertilisation. It has been known for some time that the quality of the follicular environment determines, in part, the developmental potential of the egg. Recent studies in mice have shown that the interaction between the egg and the follicle is in fact a two-way process, and that the egg is able to influence development of the ....Mammalian eggs grow and develop in fluid filled sacks in the ovary called follicles. These structures nurture the egg for prolonged periods preparing it for ovulation and fertilisation. It has been known for some time that the quality of the follicular environment determines, in part, the developmental potential of the egg. Recent studies in mice have shown that the interaction between the egg and the follicle is in fact a two-way process, and that the egg is able to influence development of the follicle. This project proposes to investigate these processes further in the laboratory mouse using new reagents available to us, and to extend these findings by investigating this communication pathway for the first time in a primate species. Because of the difficulty of undertaking such research using human material, we will use the marmoset monkey as a model. This exciting new development has important implications for women's health because it may help us understand why some women suffer from premature menopause or cystic ovaries, and in the longer term could help in the development of new types of contraceptives.Read moreRead less
Therapeutic Potential Of Transforming Growth Factor-beta Proteins For The Diagnosis And Treatment Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$942,961.00
Summary
We discovered and manufactured a growth factor produced uniquely by the egg. We named this growth factor cumulin. It is a powerful regulator of ovarian function and egg quality. This project will study the basic mechanisms of how cumulin works in the ovary. We will then develop an assay to measure it as a biomarker of human egg quality and quantity. New approaches in fertility preservation for cancer survivors will be developed using cumulin.
Prevention Of Placental Oxidative Stress And Inflammation By Dietary Omega-3 Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Several pregnancy disorders that result in low birthweight involve aberrant function of the placenta. In this project we will examine one of the key mechanisms underlying placental dysfunction, namely oxidative stress, and determine whether its adverse effects can be limited by supplementation with dietary omega 3 fatty acids. The outcomes of this project will help guide future clinical studies on the possible beneficial effects of omega-3 fatty acids in pregnancy.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
I am a reproductive biologist - reproductive immunologist investigating the role of the female immune response and its cellular and molecular agents in establishing pregnancy. My research spans basic science and clinical and commercial transfer, and aims to improve our understanding of the factors determining optimal reproductive health in women leading to better treatments for infertility and pathologies of pregnancy, and the best possible health outcomes for babies and children.