Elucidating The Role Of Epididymosomes In The Transfer Of Fertility-modulating Proteins And Regulatory Classes Of RNA To Maturing Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$539,425.00
Summary
Sperm dysfunction represents a major underlying aetiology associated with male infertility. This proposal seeks to understand the mechanisms responsible for driving the functional maturation of spermatozoa and how these mechanisms are perturbed in response to environmental stressors.
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
Why Is Trophoblast Invasion Defective In Human Pregnancies That Develop Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$504,500.00
Summary
Pre-eclampsia is the most common serious medical disorder of otherwise healthy young pregnant women. Early in pregnancies destined for pre-eclampsia, placental cells (cytotrophoblasts) do not invade deeply enough into maternal blood vessels within the uterus, with resultant low oxygen levels and reduced blood flow from the mother's circulation to placenta. This causes fetal under-nutrition and growth restriction, which if severe, can cause intrauterine death. To prevent this, the baby may need t ....Pre-eclampsia is the most common serious medical disorder of otherwise healthy young pregnant women. Early in pregnancies destined for pre-eclampsia, placental cells (cytotrophoblasts) do not invade deeply enough into maternal blood vessels within the uterus, with resultant low oxygen levels and reduced blood flow from the mother's circulation to placenta. This causes fetal under-nutrition and growth restriction, which if severe, can cause intrauterine death. To prevent this, the baby may need to be delivered prematurely, with grave risks of complications, both short and longterm. Women with pre-elampsia suffer from hypertension, activation of the clotting system, and generalized constriction of blood vessels. Together, these result in damage to blood vessel lining cells, reduced blood flow to, and disturbed function of many organs. Most commonly affected are kidney, liver, brain, and the uterine circulation. Babies born early and-or small-for-gestational-age have an increased incidence of vascular disease, hypertension, diabetes and kidney disease in adult life. Improved understanding, and development of preventive and-or therapeutic strategies for pre-eclampsia are urgently needed. There is no satisfactory animal model to address pathogenesis of this peculiarly human disorder, which concurrently causes significant morbidity in two generations of people. Ethical constraints and the need for urgent therapy limit extensive research in affected pregnant women. With our unique in vitro cell co-culture strategy, we have clarified inter-relationships between fetal-placental cells (cytotrophoblasts) and their host maternal vascular cells (decidual endothelial cells) in the clinical syndrome of pre-eclampsia. Building on this work we will now examine maternal-placental intercellular cooperation in regulation of normal placental development, and explore the defective regulation of placental development that precedes pre-eclampsia.Read moreRead less
The Role Of FSH And FF-MAS In The Induction Of Meiotic Resumption In The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order ....About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order to produce many eggs, thereby increasing the success rate per treatment cycle. But stimulation of ovarian function involves a number of drawbacks including cost of fertility drugs, continued monitoring, discomfort and risk of complications (eg. ovarian hyperstimulation syndrome). It is evident that novel methods for the production of mature eggs in vitro in the absence of ovarian stimulation would mark a breakthrough, making assisted reproduction a more friendly discipline. In general, all IVF patients would benefit from in vitro maturation techniques. In particular, in selected patients (eg. those suffering from polycystic ovary syndrome) the advantages of this method might prove to be invaluable, by achieving production of fully viable eggs under controlled conditions, as opposed to in vivo where oocytes generally fail to acquire full competence, having been subjected to an unfavourable hormonal environment. Unfortunately, attempts to treat IVF patients using eggs matured in vitro has been disappointing so far, with only occasional pregnancies reported over the last decade. Clearly, this is due to lack of knowledge of the fundamental events occurring during egg maturation, as well as the paucity of biological material available for experimentation. So, to make in vitro maturation of eggs a successful fertility treatment we undoubtedly need to achieve a more profound insight into the function of the egg, the first step being to focus our attention upon experimental models.Read moreRead less