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.
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.
The Effects Of Pre-term Birth On The Baboon And Human Neonatal Kidney
Funder
National Health and Medical Research Council
Funding Amount
$349,248.00
Summary
LAY DESCRIPTION: Over the past two decades the incidence and survival after pre-term birth has increased substantially. Despite significant improvements in the treatment of these pre-term babies there remains a high incidence of kidney failure. The functional unit of the kidney is the nephron and they are formed in the kidney late in pregnancy at a time when many preterm babies are already delivered. Hence, it is important to determine what is the effect of preterm birth on the formation of neph ....LAY DESCRIPTION: Over the past two decades the incidence and survival after pre-term birth has increased substantially. Despite significant improvements in the treatment of these pre-term babies there remains a high incidence of kidney failure. The functional unit of the kidney is the nephron and they are formed in the kidney late in pregnancy at a time when many preterm babies are already delivered. Hence, it is important to determine what is the effect of preterm birth on the formation of nephrons. We have shown that the baboon is an excellent model of kidney development in humans. Like humans, we can prematurely deliver baboons and maintain them in a neonatal intensive care unit after birth. In this model, we have evidence to suggest that the formation of the the nephrons within the kidneys of the pre-term infants is impaired and we predict that this leads to impaired kidney function after birth and to susceptibility for renal disease in adulthood. In this study, we will examine kidney function in preterm baboon and human babies and also undertake studies in autopsied kidneys from baboon and human pre-term infants. We will determine whether the number and the cellular structure of the nephrons is affected by preterm delivery and if so, whether kidney function is affected. By comprehensively examining the medical records of the mother and babies, we also aim to identify factors in the care of the mother prior to birth, or of the baby after birth which may link to impaired nephron formation and kidney dysfunction in the baby. We will also determine whether administration of retinoic acid to the baboon preterm baby soon after birth can stimulate the formation of nephrons. The findings of this study will provide important new insights into the mechanisms of kidne failure in preterm babies and will identify potential strategies to prevent nephron loss and enhance nephron formation in preterm infants, which will in turn have long-term implications to kidney health.Read moreRead less