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
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.
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
I seek the knowledge required to improve prevention, diagnosis and therapy for men with testicular pathologies by studying what controls early sperm development. My research will delineate how cellular signalling molecules lay the foundation for adult fertility, using animal studies, cell culture and clinical samples. Testis samples from testicular cancer patients will be used to test interventions that may kill tumour cells or offer a therapeutic option to men with impaired spermatogenesis.
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.
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
Translating Oocyte Biology Discoveries To New Clinical Practices
Funder
National Health and Medical Research Council
Funding Amount
$772,605.00
Summary
A/Professor Gilchrist is a reproductive biologist studying factors that regulate the intrinsic quality of unfertilised eggs. He has produced and patented the use of unique growth factors produced by the egg that enhance egg quality in women. Bringing together industry and a world-leading clinic, he is developing new forms of hormone-free infertility treatment which he will take to clinical practice over the next 5 years.
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