The Male Partner Contribution To Pregnancy Immune Tolerance Deficit In Women
Funder
National Health and Medical Research Council
Funding Amount
$1,462,925.00
Summary
A complication-free pregnancy and birth of a healthy infant depends on adequate preparation of the mother's immune system to tolerate the 'foreign' fetus, Both the mother and the father contribute to establishing optimal immune tolerance. This project will determine the links between specific agents in male seminal fluid and the female immune response, and will make progress towards new diagnostic tests and treatment options for unexplained subfertility and gestational disorders.
The Role Of Stem-progenitor Cells In Regeneration Of Mouse Endometrium.
Funder
National Health and Medical Research Council
Funding Amount
$311,938.00
Summary
The endometrium (lining of the uterus) undergoes breakdown and re-growth each month as part of the menstrual cycle. This restorative process is not well understood. For the first time stem cells have been identified within human endometrium that are likely to be responsible for its remarkable regeneration. The aim of this project is to identify stem cells within the mouse endometrium, to use as a model to understand how the endometrium restores each month after menstruation.
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