Immunobiology Of Early Pregnancy - A Model Of Virus-induced Abortion
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft trans ....The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft transplantation. Infection with flaviviruses increases the concentrations of cell surface self and adhesion molecules in vertebrate cells, including the trophoblast cells of the placenta. As a result, these molecules can then be recognised by the maternal immune system and the embryo targeted for destruction. We hypothesise that the induction of these molecules by this and other viruses may break the immunological silence of the early embryo and reverse the local suppression of the maternal immune response. This would result in maternal immune rejection of the embryo and abortion. This initial sensitisation of the mother by the virus might be one of the reasons that some women suffer recurrent abortions. We will use a novel viral mouse model where we implant virus-infected embryos into receptive animals to enable us to dissect out the unusual requirements for induction of maternal anti-viral immunity during pregnancy. This model was developed in our laboratory to directly test our hypotheses. It does not cause systemic illness in the mother which itself can lead to non-specific abortion. This model therefore can for the first time elucidate the specific mechanisms associated with the delicate balance between eradicating virus and maintaining pregnancy. Results from this project will inform rational design of treatment of recurrent abortions in the community.Read moreRead less
I am a reproductive biologist focused on women’s reproductive health. I am studying the reasons why some women are infertile have spontaneous abortions and pregnancy complications such as pre-eclampsia. My research will define the roles of molecules that are critical in the establishment of pregnancy and the formation of a health placenta and therefore a healthy baby.
The AusCAPPS Network: A Community Of Practice To Support The Provision Of Long Acting Reversible Contraception And Medical Termination Of Pregnancy In Primary Care
Funder
National Health and Medical Research Council
Funding Amount
$1,207,160.00
Summary
The Australian Contraception and Abortion Primary Care Practitioner Support (AusCAPPS) Network aims to provide much needed support to general practitioners, pharmacists and nurses working in primary care to improve the delivery of long acting reversible contraception and medical termination of pregnancy to Australian women. Increasing the delivery and access to these services in primary care will decrease unintended pregnancies and improve health outcomes for Australian women.
Preterm birth, a birth before the 37th week of pregnancy occurs for fewer than 8% of mothers but is associated with two-thirds of all fetal deaths and deaths of liveborn infants in the first month after birth. In the late 1990s those deaths are concentrated among very preterm births i.e. births before the 32nd week of pregnancy. Infants born very preterm are very likely to need neonatal intensive care, quite likely to have had major respiratory, infectious or other problems after birth, and to n ....Preterm birth, a birth before the 37th week of pregnancy occurs for fewer than 8% of mothers but is associated with two-thirds of all fetal deaths and deaths of liveborn infants in the first month after birth. In the late 1990s those deaths are concentrated among very preterm births i.e. births before the 32nd week of pregnancy. Infants born very preterm are very likely to need neonatal intensive care, quite likely to have had major respiratory, infectious or other problems after birth, and to need readmission to hospital in the first year after birth. Surviving infants are more likely to have major impairments, minor impairments, and school difficulties than infants born at term. There is a substantial impact on families, health services and society of very preterm birth.There has been no reduction in the proportion of births which are preterm, or very preterm in the last 20 years, though advances in treatment and care have markedly improved the survival of preterm and very preterm infants. This study will investigate the role of previous pregnancies which did not result in births (miscarriages and terminations), together with other procedures such as D and C (dilatation and curettage), in subsequent preterm birth. As these previous pregnancy losses are all fairly common experiences any associated risk is important and this particular factor has not been studied in this way before. There is preliminary evidence that they may be associated with preterm birth and the study will be able to measure the associations while taking into account all the other known risk factors. Other possible risk factors such as experiencing violence in pregnancy or social factors acting at a neighbourhood level will also be included. If it is found that previous pregnancy losses are independently associated with preterm birth it will be possible to develop and test preventive strategies.Read moreRead less
The Early Origins Of Obsteric Diseases: Biological Investigations And Biomarker Discovery
Funder
National Health and Medical Research Council
Funding Amount
$282,290.00
Summary
Recent evidence has pointed to the beginning of pregnancy as the time when biological cascades begin that cause common diseases of pregnancy. This opens the door to developing bloods test in early pregnancy predicting who will develop problems, and to hunt for novel proteins in the bloodstream that are causing the illnesses. 'Proteomic technology' will be used, a new cutting edge tool that can scan the entire protein pool in mum's blood in a single experiment.
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
Complement C5a Receptors , Placental Inflammation And Reproductive Impairment.
Funder
National Health and Medical Research Council
Funding Amount
$1,025,229.00
Summary
We are investigating how mothers may have health difficulties during pregnancy, such as high blood pressure, and how this can affect their fetuses' health. There is emerging evidence that an unhealthy placenta during pregnancy can greatly affect fetal development, and it seems that inflammation in the placenta during pregnancy may be a key factor in reducing fetal growth, resulting in low birth weight infants. Our studies are aimed at developing new treatments for this.
The starting point for this project is the recent finding that women who experience miscarriages or terminations of pregnancy before theuir first birth have an increased risk of having a preterm (premature) infant. These findings have prompted a re-evaluation of the relationship between the number of pregnancies a women has had and the likely outcome in later pregnancies. It will take into account the stage at which prior pregnancies ended, what the outcomes of the pregnancies were (birth, healt ....The starting point for this project is the recent finding that women who experience miscarriages or terminations of pregnancy before theuir first birth have an increased risk of having a preterm (premature) infant. These findings have prompted a re-evaluation of the relationship between the number of pregnancies a women has had and the likely outcome in later pregnancies. It will take into account the stage at which prior pregnancies ended, what the outcomes of the pregnancies were (birth, health baby, death, baby with a birth defect, termination, miscarriage etc), as well as factors such as maternal age, in relation to the risks in subsequent pregnancies. The expected outcomes and significance of the study are: * new evidence about factors causing adverse outcomes of pregnancy; * better information on the risk of recuurence of common birth defects; * more precise information on risks of adverse pregnancy outcomes for users and planners of maternity services.Read moreRead less