Epigenetics Of Human Placental Development And Pregnancy-associated Disease.
Funder
National Health and Medical Research Council
Funding Amount
$85,526.00
Summary
Mounting evidence suggests that epigenetic changes such as DNA methylation during pregnancy may play an important role in adverse pregnancy outcomes and modulation of disease risk later in life. We have identified a range of distinct DNA methylation events in human placental cells that are likely to play a role in both normal human placentation and aspects of placental dysfunction. We believe that disruption of this epigenetic profile contributes to adverse pregnancy outcomes
The Role Of Oxygen Sensing In The Regulation Of Trophoblast Invasion
Funder
National Health and Medical Research Council
Funding Amount
$404,323.00
Summary
Normal fetal development requires the placenta to successfully invade the mother's uterus so that the baby can be appropriately nourished. It is well known that a failure of normal placental development is associated with two major complications of pregnancy: pre-eclampsia and intrauterine growth restriction. This study is designed to discover whether placental cells have special oxygen sensing mechanisms that help them home in to areas where there is high oxygen.
Understanding Immune Tolerance In Pregnancy To Discover A New Intervention For The Treatment Of Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$492,202.00
Summary
Pre-eclampsia is a common complication of pregnancy. Women who develop pre-eclampsia experience high blood pressure, swelling and lose protein in the urine. There is no treatment for pre-eclampsia other than delivery of the baby. Pre-eclampsia has risks for the mother and the baby. This research will discover whether generalised inflammation in the mother is a cause of pre-eclampsia and will evaluate the role of a novel treatment for its potential to prevent this life threatening condition.
Focus On The Uterus: Basic And Translational Research Strategies To Address Key Issues In Women’s Health. Fertility, Infertility, Endometrial And Pregnancy Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$1,085,790.00
Summary
My work focuses on the endometrium, the lining of the uterus, into which the embryo implants to establish pregnancy. When the endometrium does not function correctly, the woman is usually infertile. Other disorders of the endometrium include endometriosis, menstrual bleeding problems and cancer. My studies have defined the molecular basis for much endometrial dysfunction. I am now developing non-invasive tests for these problems and rationales for new treatments.
Novel Roles For Follistatin In Reproductive Biology
Funder
National Health and Medical Research Council
Funding Amount
$630,916.00
Summary
The follistatin protein has important functions throughout the body. Recent studies using mutant mice have identified key roles for follistatin in the development and function of the female reproductive system (ovary, uterus). We will now undertake detailed studies to determine how follistatin regulates these processes. This is relevant to our understanding of the mechanisms causing infection and inflammation in the reproductive tract.
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
This study aims to determine the extent to which semen is important in initiating the maternal immune response to the fetus and placenta during pregnancy. We postulate that exposure to paternal proteins in sperm and other factors present in the semen may have a cumulative, beneficial effect in 'educating' the female immune system to respond in the correct way to the embryo when pregnancy occurs. To investigate this, the behaviour and movements of white blood cells responding to semen will be stu ....This study aims to determine the extent to which semen is important in initiating the maternal immune response to the fetus and placenta during pregnancy. We postulate that exposure to paternal proteins in sperm and other factors present in the semen may have a cumulative, beneficial effect in 'educating' the female immune system to respond in the correct way to the embryo when pregnancy occurs. To investigate this, the behaviour and movements of white blood cells responding to semen will be studied during the period after mating, in which the uterus prepares for and accommodates to pregnancy. In particular, the study will focus on the roles of a specific chemical messenger substance in semen, called transforming growth factor (TGF)-beta, which triggers the molecular changes leading to maternal immune tolerance. A deeper understanding of these events will have an important impact in human and veterinary medicine where implantation failure is a major cause of reproductive loss and inadequate placental growth poses a threat to the health of the conceptus both in utero and into adult life.Read moreRead less
Why Is Trophoblast Invasion Defective In Human Pregnancies That Develop Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$504,500.00
Summary
Pre-eclampsia is the most common serious medical disorder of otherwise healthy young pregnant women. Early in pregnancies destined for pre-eclampsia, placental cells (cytotrophoblasts) do not invade deeply enough into maternal blood vessels within the uterus, with resultant low oxygen levels and reduced blood flow from the mother's circulation to placenta. This causes fetal under-nutrition and growth restriction, which if severe, can cause intrauterine death. To prevent this, the baby may need t ....Pre-eclampsia is the most common serious medical disorder of otherwise healthy young pregnant women. Early in pregnancies destined for pre-eclampsia, placental cells (cytotrophoblasts) do not invade deeply enough into maternal blood vessels within the uterus, with resultant low oxygen levels and reduced blood flow from the mother's circulation to placenta. This causes fetal under-nutrition and growth restriction, which if severe, can cause intrauterine death. To prevent this, the baby may need to be delivered prematurely, with grave risks of complications, both short and longterm. Women with pre-elampsia suffer from hypertension, activation of the clotting system, and generalized constriction of blood vessels. Together, these result in damage to blood vessel lining cells, reduced blood flow to, and disturbed function of many organs. Most commonly affected are kidney, liver, brain, and the uterine circulation. Babies born early and-or small-for-gestational-age have an increased incidence of vascular disease, hypertension, diabetes and kidney disease in adult life. Improved understanding, and development of preventive and-or therapeutic strategies for pre-eclampsia are urgently needed. There is no satisfactory animal model to address pathogenesis of this peculiarly human disorder, which concurrently causes significant morbidity in two generations of people. Ethical constraints and the need for urgent therapy limit extensive research in affected pregnant women. With our unique in vitro cell co-culture strategy, we have clarified inter-relationships between fetal-placental cells (cytotrophoblasts) and their host maternal vascular cells (decidual endothelial cells) in the clinical syndrome of pre-eclampsia. Building on this work we will now examine maternal-placental intercellular cooperation in regulation of normal placental development, and explore the defective regulation of placental development that precedes pre-eclampsia.Read moreRead less