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
Diet And Exercise Intervention For Paternal Obesity Improves Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$678,481.00
Summary
Obesity is a growing problem in Western Society and is associated with a large number of metabolic conditions. There is an increasing awareness that a fathers health at the time of conception affects fertility and also the ongoing health of the pregnancy and the ofspring. This study seeks to determine if diet and exercise intervention for overweight or obese males can improve the health of the sperm and therefore the ability to father a pregnancy and the health of the offspring.
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
The Function Of Gametogenenin In Male Fertility And Embryogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,579.00
Summary
We have identified gametogenetin as novel protein involved in sperm production and in the very earliest stages of embryo survival. It is found within the sperm tail where it binds to cysteine-rich secretory protein 2. The aim of this project is to further refine the biochemistry of GGN using a combination of binding studies, expression analyses and the characterization of two unique mouse models. This project has direct relevance to the causes of human infertility and contraceptive development.