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.
Epithelial-trophoblast Interactions In Human Embryo Implantation: Role For Interleukin 11 And Leukemia Inhibitory Factor
Funder
National Health and Medical Research Council
Funding Amount
$495,667.00
Summary
Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Female infertility is frequently due to implantation failure and many IVF embryos fail to implant. Appropriate development of the placenta is critical to the outcome of pregnancy and inadequate placentation can result in spontaneous abortion. However, if the pregnancy continues with a poorly developed placenta, the mother is likely to develop pre-eclampsia with subsequent major adverse outcomes for both mother and b ....Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Female infertility is frequently due to implantation failure and many IVF embryos fail to implant. Appropriate development of the placenta is critical to the outcome of pregnancy and inadequate placentation can result in spontaneous abortion. However, if the pregnancy continues with a poorly developed placenta, the mother is likely to develop pre-eclampsia with subsequent major adverse outcomes for both mother and baby. Pre-clampsia is the most common cause of low birth weight infants and also of maternal death. Low birth weight, which is commonly an outcome of a pregnancy with pre-eclampsia, correlates with disorders later in life (including hypertension, diabetes, coronary heart disease and obesity). Interleukin (IL)-11 and leukemia inhibitory factor (LIF) are among very few molecules known to be critical for embryo implantation in the mouse. Their roles in human infertility are not well understood, although there is evidence that decreased LIF is associated with implantation failure in women. The distribution of these molecules within the uterus and placenta in primates suggests they have important roles in preparing the uterine lining for implantation and for development of a placenta in women. This project will examine how IL-11 and LIF that are locally produced at implantation sites affect the human uterus and the formation of the placenta. There is still no means of readily diagnosing endometrial infertility in women or of establishing whether the placenta is developing adequately. These studies will provide new critical information regarding the roles of these two molecules and their potential usefulness as targets for much- needed diagnostic and therapeutic tools for infertility and major diseases associated with pregnancy. Application of such new tests will produce lifelong benefits to the health of both the mother and child.Read moreRead less
Leucine-rich Guanylate Kinase Is A Regulator Of Sperm Tail Development And Motile Cilia Function
Funder
National Health and Medical Research Council
Funding Amount
$540,191.00
Summary
In this grant we will define the function of an uncharacterized protein, LRGUK, in fertility and hydrocephalus (water on the brain). LRGUK has a critical role in sperm development. We will define the cell biology and biochemistry of LRGUK function, we will assess the incidence of LRGUK mutations in human fertility and explore LRGUK function in the brain. Data obtained will have relevance to the 1 in 20 young men who suffer from infertility and the 3 in 1000 children who develop hydrocephalus.
Kisspeptin And Its Receptor Mastermind Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Reproduction is controlled by the brain and gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. Finding critical regulators of GnRH has remained the most important goal for reproductive endocrinologists for over 30 years. The brain peptide hormone called kisspeptin and its receptor Kiss1R appear vital in the control of reproduction. This project will detail the role kisspeptin and Kiss1R play in controlling hormones from the brain that govern puberty and reproduction.
Katanin P80 Is A Key Regulator Of Microtubule Dynamics And Male Fertility.
Funder
National Health and Medical Research Council
Funding Amount
$603,756.00
Summary
Male fertility is a complex process requiring the co-ordinated activation of thousands of gene products. It is not surprising therefore that 1 in 15 Australian men are infertile. This project will explore an essential pathways for sperm production, specifically related to sperm shaping and motility. This work may ultimately have implications for the diagnosis and treatment of male infertility, but also for pathology in tissues will similar cellular structures.
The failure of an embryo to implant is a major cause of infertility. While IVF is an important intervention, still three quarters of embryos do not implant. We have identified new factors that we believe are critically important in embryo attachment to the womb. We will now prove whether these factors are critical and therefore provide the evidence required to begin to develop novel treatment options for infertility.
Gonadotropin Inhibitory Hormone As A Major Regulator Of Reproduction In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$623,378.00
Summary
Reproduction is controlled by the brain and it has been well established that gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. GnRH stimulates the pituitary gland to produce and secrete hormones that, in turn, stimulate the ovaries and testes. It is becoming clear that the brain also produces an inhibitory factor and this project aims to establish that it (gonadotropin inhibitory hormone; GnIH) is functional in mammals.
Cohesin: Role In Germ Cell Chromosomal Segregation
Funder
National Health and Medical Research Council
Funding Amount
$435,526.00
Summary
At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related gen ....At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related genes, called Rec8 and Rad21, which we recently discovered in humans and mice. Due to that these genes are essential for chromosome separation in other species and they exists in species as diverse as yeast and humans, they may be responsible for accurate separation of chromosomes in germ cells in mammals. In this proposal, we will determine the role(s) of these molecules in controlling proper chromosome segregation by loss-of-function studies in genetically engineered mice lacking Rec8 and Rad21 genes. By analyzing the chromosomal abnormalities of the cells from these animals, we will gain critical information about the nature of chromosome partitioning disorders in humans.Read moreRead less
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.