Novel Actions Of Leptin In Implantation And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of f ....The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of fetal growth. In human pregnancy, the placenta becomes an additional major source of leptin, and this is secreted into the mother and the fetus. Recent work in animal models also indicates that the process of implantation, whereby the embryo embeds itself in the lining of the uterus and establishes a placenta, cannot proceed in the absence of leptin. But how leptin exerts these critical effects on the implantation process and placental function is not known. In this study we will explore several potential actions of leptin in the uterus and placenta, and examine whether the leptin signaling system is aberrant in cases where the fetus does not grow normally. Of particular interest is the possible interaction of leptin with another group of important signaling molecules called the peroxisome proliferator-activated receptors, or PPARs. One of these, PPAR-gamma, plays an indispensable role in the establishment of the placenta, particularly in relation to the formation of blood vessels, a process that is also a target for leptin action. Several lines of evidence, most notably in fat cells, suggest that both PPAR-gamma and leptin regulate common aspects of cell function. Such interactions provide us with important clues as to how leptin and the PPARs could work together to promote the optimal establishment, growth and function of the placenta, and these will be explored in this project.Read moreRead less
Endometrial Receptivity For Embryo Implantation: Proprotein Convertase 6 And Plasma Membrane Remodeling
Funder
National Health and Medical Research Council
Funding Amount
$631,344.00
Summary
Implantation of an embryo into the uterus is a key step in establishing pregnancy; it requires a receptive uterus (fertile soil) and a healthy embryo (seed). Implantation failure causes pregnancy loss and infertility, and is also a major limiting factor in IVF. We have established that proprotein convertase 6 (PC6) is a master regulator of uterine receptivity for implantation. We will investigate how PC6 works in a woman’s uterus, and how we can use this knowledge to improve implantation in IVF.
Successful establishment of pregnancy requires a viable embryo and a receptive uterus. The contribution that reduced uterine receptivity makes to human infertility is unknown. IVF patients with implantation failure will be investigated using different approaches to identify gene pathways that are altered in reduced uterine receptivity. This study could lead to a clinical test for uterine receptivity and help to improve fertility treatment options for women with repeated implantation failure.
Determinants Of Reproductive Health: Basic And Translational Studies In Fertility.
Funder
National Health and Medical Research Council
Funding Amount
$12,530,124.00
Summary
Reproductive health is an issue of national and international significance yet there are considerable unmet needs in the key areas of infertility and contraception. The health of each adult is strongly affected by very early events in development, including the effects of genetics and environment on sperm and eggs, and of the intra-uterine environment. This program will use a combination of advanced technologies to address these issues and will translate findings to the clinic, thus improving th ....Reproductive health is an issue of national and international significance yet there are considerable unmet needs in the key areas of infertility and contraception. The health of each adult is strongly affected by very early events in development, including the effects of genetics and environment on sperm and eggs, and of the intra-uterine environment. This program will use a combination of advanced technologies to address these issues and will translate findings to the clinic, thus improving the quality of reproductive health care and the long-term health of Australians.Read moreRead less
Peri-conception Determinants Of Reproductive And Pregnancy Health
Funder
National Health and Medical Research Council
Funding Amount
$3,560,520.00
Summary
Reproductive and pregnancy disorders are common in Australian men and women, with 6% couples seeking infertility services and another 30% experiencing recurrent miscarriage, preeclampsia or preterm birth, often resulting in life-time health problems for children, and sometimes stillbirth. This research will investigate the immune causes of these conditions, and the results will contribute to new health tools, diagnostics and medical treatments to support maternal and infant health.
Interleukin 11 And Leukaemia Inhibitory Factor: Important Regulators Of Embryo Implantation And Placentation
Funder
National Health and Medical Research Council
Funding Amount
$346,117.00
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 roles in women are unknown. I 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.
Decidual-trophoblast Interactions Critical For Optimal Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$612,927.00
Summary
This proposal seeks to identify the critical maternal and embryonic placental factors that regulate the formation of a healthy placenta and thus a healthy pregnancy and baby. Currently there is no way of identifying whether the placenta is forming adequately. The proposed studies are a necessary first step in identifying therapeutic targets for diseases associated with a poorly formed placenta, such as preeclampsia.