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Novel Analogues Of Human INSL3 As Antagonists And Probes Of Testicular Function
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
The hormone, insulin-like peptide 3, has recently been shown to act directly on male and female germ cells to cause their maturation. It has considerable promise as a therapeutic agent for the regulation of fertility. Drugs based on the peptide may be used to assist in cases of infertility, and drugs that block its action have great potential as male and female contraceptives. Towards these goals, our project aims to understand how this peptide exerts its unique biological effects.
Studies Of The Paracrine Role Of Inhibin A/activin A In Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enor ....This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enormous difference to women s health in the following areas: contraception, the possibility of development of new methods of contraception that block egg release without affecting the normal ovarian cycle endocrinology; fertility treatment, better methods of obtaining mature oocytes without subjecting women to high dose gonadotrophin treatment and the accompanying sequelae; improving knowledge of the factors that promote satisfactory oocyte maturation and embryo development so that with improved implantation rates, fewer embryos need be replaced to achieve a pregnancy.Read moreRead less
Cumulus Cell Invasive Migration: Clearing A Path For The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$409,684.00
Summary
Ovulation is the process by which the egg is released from a female�s ovary, but it is not known how this process is controlled. We found that cells surrounding the egg are motile and similar to cancer cells; thus we hypothesize that this enables the egg to _invade� its way out of the ovary. We will test this idea in mice and determine whether similar processes are happening in women. The results will provide new information about how to stop ovulation and aid women who experience infertility.
Proprotein Convertase 6: A Master Regulator For The Development Of Endometrial Receptivity And Embryo Implantation
Funder
National Health and Medical Research Council
Funding Amount
$424,846.00
Summary
Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in sponta ....Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in spontaneous abortion. How the uterus becomes receptive is not well understood. Our recent research has identified that proprotein convertase 6 (PC6), an important master switch responsible for activating other proteins, is tightly regulated in the uterus during its preparation for receptivity and critical for implantation. This project will examine how PC6 acts in the human uterus to make it receptive, by identifying the factors that PC6 controls and how this controlling works. We will use a cell culture model with cells isolated from human term placenta. In addition, there is no means of readily testing whether the uterus is receptive owing to the lack of reliable biomarkers. In this study we will determine whether PC6 (and those molecules controlled by PC6) are potential biomarkers for uterine receptivity. This will be achieved by examining uterine biopsies and uterine washings collected from proven fertile volunteers and patients of proven endometrial infertility. This study will greatly enhance our understanding of how a critical molecule, PC6, acts in the uterus for implantation. The results will provide new knowledge regarding uterine preparation for implantation. The study has considerable implication for developing much-needed diagnostic and therapeutic tools for uterine receptivity and infertility.Read moreRead less
Interleukin 11 And Leukemia Inhibitory Factor: Pivotal Regulators Of Uterine Receptivity And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Interleukin (IL)-11 and leukemia inhibitory factor (LIF) are critical for embryo implantation in mice but their mechanisms of action in women are not well defined. We will define their roles in the establishment of pregnancy and provide new critical information on their potential as targets for diagnostic and therapeutic tools for infertility and major diseases associated with pregnancy.
Critical Role Of Proprotein Convertase 6 In Human Uterine Epithelium For Embryo Implantation And Clinical Implications
Funder
National Health and Medical Research Council
Funding Amount
$643,899.00
Summary
Implantation of an embryo into the uterus is a key step for human development. Implantation failure causes embryonic death, pregnancy loss and infertility. Conversely, preventing implantation is an attractive approach for contraception. We have established that proprotein convertase 6 (PC6) is a master regulator of implantation. We will investigate how PC6 works in a woman's uterus, and how we can use this knowledge to improve implantation in IVF and to develop PC6 drugs for new contraceptives.
Redox Cycling Of Quinones By Human Spermatozoa: A Potential Strategy For The Dual Regulation Of Fertility And STDs
Funder
National Health and Medical Research Council
Funding Amount
$314,625.00
Summary
The purpose of this research project is to develop a novel form of contraception that could meet the dual objectives of fertility regulation and prevention of sexually transmitted disease (STD). A particularly novel feature of this proposed spermicide-microbicide is that it has to be activated by spermatozoa i.e the formulation comprises a pro-spermicide that only generates the active principle on contact with sperm. This aspect of the method sets it apart from all other forms of topical contrac ....The purpose of this research project is to develop a novel form of contraception that could meet the dual objectives of fertility regulation and prevention of sexually transmitted disease (STD). A particularly novel feature of this proposed spermicide-microbicide is that it has to be activated by spermatozoa i.e the formulation comprises a pro-spermicide that only generates the active principle on contact with sperm. This aspect of the method sets it apart from all other forms of topical contraception because unlike barrier methods and vaginal creams or foams, its use will not be coitus related. Ultimately it is envisaged that the product could be incorporated into a soft pliable vaginal sponge and left in situ until such time as it becomes activated following intercourse. Such a method should be particularly acceptable to young women who are vulnerable to both STDs and unwanted pregnancy as indicated by (a) the relatively high rates of STDs in adolescent girls, particularly in the indigenous community, and (b) the fact that 50% of all recorded pregnancies to Australian women under 19 years of age end in abortion. The method exploits the susceptibility of human spermatozoa and pathogenic organisms responsible for STDs to oxidative stress and, in effect, mimics a naturally occurring cause of male infertility. If successful, this project would produce a female centred method of contraception and STD prevention that would revolutionize reproductive health care for young women worldwide, as well as generating intellectual property of considerable potential value to the nation.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
Macrophages In Developmental Programming Of Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$532,386.00
Summary
Programming of reproductive health in women begins long before sexual maturity. Development during childhood, puberty and adulthood produces a fully functional reproductive system capable of conceiving, gestating and nurturing a child. This project will investigate the role of immune cells known as macrophages in the reproductive system, and investigate how their disruption might influence developmental programming and have lifetime consequences for the reproductive health of the individual.
This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.