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.
HtrA4-induced Endothelial Dysfunction In Early-onset Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$86,073.00
Summary
Preeclampsia (PE), a life-threatening disorder of pregnancy, is characterized by a sudden increase in blood pressure in association with wide-spread endothelial dysfunction. Placenta-derived factors are believed to cause PE development. Our recent studies have identified that HtrA4, a placenta-specific serine protease may contribute to endothelial dysfunction. This study will investigate the mechanisms of HtrA4-induced endothelial dysfunction.
Cell-cell fusion is critical for the development and transport capacity of the placenta during pregnancy. Impairments in this process occur in pregnancy complications such as preeclampsia (PE). We have identified a novel pathway (LY6E) regulating placental cell-cell fusion which is also dysregulated in human pregnancies complicated by PE. In the current proposal we will investigate the mechanisms by which LY6E mediates cell-cell fusion and examine its role in the development of PE.
Placental Malaria, Placental Function, Nutrient Transport And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$483,517.00
Summary
Malaria infection in the placenta impairs the baby's growth, probably by causing placental inflammation. We believe this inflammation interferes with the ability of placental cells to transport nutrients such as amino acids and glucose from mother to baby. We will test this by examining the expression of genes and proteins involved in nutrient transport in placental samples from pregnant women, and in cell lines, and will examine how malaria affects growth factors that control this process.
Novel Molecular Pathways Of The Placental Renin Angiotensin System In Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$323,524.00
Summary
Preeclampsia (PE) is a common and potentially life-threatening pregnancy disorder of pregnancy which originates in the early placenta. We will look into new interactions between molecules that determine how early cells establish a functioning placenta. Detection and early treatment of abnormal placental function can prevent PE before serious complications develop.
Regulation Of The Placental Renin-angiotensin System By MicroRNAs; Implications For Pregnancies Complicated By Placental Insufficiency?
Funder
National Health and Medical Research Council
Funding Amount
$483,058.00
Summary
Intrauterine growth restriction (IUGR) and preeclampsia (PrE) are life threatening to mother and baby, making the baby susceptible to disease as an adult. One of the major causes of PreE and IUGR is placentation. Placentation is affected by the placental renin-angiotensin system (RAS), which is controlled by microRNAs. We will describe these microRNAs, what controls them; determine their expression and RAS expression in normal pregnancy, IUGR and PrE, thus providing novel biomarkers for their ea ....Intrauterine growth restriction (IUGR) and preeclampsia (PrE) are life threatening to mother and baby, making the baby susceptible to disease as an adult. One of the major causes of PreE and IUGR is placentation. Placentation is affected by the placental renin-angiotensin system (RAS), which is controlled by microRNAs. We will describe these microRNAs, what controls them; determine their expression and RAS expression in normal pregnancy, IUGR and PrE, thus providing novel biomarkers for their early detection.Read moreRead less
Implantation of an embryo into the uterus & development of a functional placenta are critical to initiate & continue a pregnancy. Implantation failure causes infertility and is a major bottle-neck in IVF. Placental insufficiency leads to pregnancy loss, under-developed fetuses & a life-threatening pregnancy-specific disease preeclampsia. This application will investigate how a woman’s uterus works for implantation and placental development, how to increase IVF success and diagnose & potentially ....Implantation of an embryo into the uterus & development of a functional placenta are critical to initiate & continue a pregnancy. Implantation failure causes infertility and is a major bottle-neck in IVF. Placental insufficiency leads to pregnancy loss, under-developed fetuses & a life-threatening pregnancy-specific disease preeclampsia. This application will investigate how a woman’s uterus works for implantation and placental development, how to increase IVF success and diagnose & potentially treat preeclampsia.Read moreRead less
Interstitially Invasive Trophoblast Of The Murine Placenta: Developmental Origins, Functions And Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$369,717.00
Summary
Due to the obvious limitations to studying human pregnancy, the mouse has become a valuable model. However, invasion of the placenta into the uterine wall and vasculature, critical for successful pregnancy, is poorly understood in the mouse. The aims of the proposal are designed to gain a better understanding of these processes in mice and will provide a more accurate model system to study serious pregnancy complications resulting from abnormal placental invasion, such as preeclampsia.
Characterisation Of Abnormal Placental Stem Cells In A Human Pregnancy Disorder
Funder
National Health and Medical Research Council
Funding Amount
$487,969.00
Summary
The placenta is a rich source of stem cells. We have discovered that stem cells from placentae affected by fetal growth restriction (FGR), a clinically significant pregnancy disorder, are morphologically and functionally different to normal placental stem cells. We predict that abnormal stem cells contribute to FGR. We will carry out gene expression and functional studies to further characterise the abnormal stem cells. The work may lead to new types of treatments for FGR in future.
The Role Of Placental Transcription Factors In The Pathogenesis Of Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$601,582.00
Summary
We must understand the role of growth control genes in the growth of the human placenta. The reason is that in several significant placental disorders, placental formation is abnormal and prevents the placenta from functioning efficiently. This in turn, impacts on the growth of the developning fetus. A variety of established and innovative methods described in this project will determine the functions of the placental growth control genes and may lead to novel therapeutic targets.