Why is trophoblast invasion defective in human pregnancies that develop pre-eclampsia

Funded Activity 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 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.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $504,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Reproduction

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

growth factors | hypoxia | maternal renal disease in pregnancy and fetal health | matrix metalloproteinases | pathogenic mechanisms | placental implantation | pre-eclampsia | tissue development | trophoblast invasion

Related Links