Placenta and vascular biology

Normal placental development is key to pregnancy success.

A condition known as pre-eclampsia is a complication of pregnancy and occurs as a result of a disorder relating to human placentation. Statistically, this condition is apparent in a certain percentage of pregnancies and is a potential cause of death for both mothers and babies.

The Perinatal Research Group has pioneered a technique to allow the investigation of trophoblast function early in human pregnancy by collecting tissue from a normal ongoing gestation. As such, our research group:

• Have successfully characterised trophoblast populations from chorionic villus samples (CVS) collected from ongoing pregnancies
• Have established a robust model of assessing trophoblast function in normal and pathological pregnancies using trophoblast cells from these samples
• Are currently determining the effect of oxygen tension on the expression of inflammatory, angiogenic and migratory markers in the development and function of trophoblast from normal and pathological pregnancies.

This work will discover new knowledge about the control of trophoblast differentiation and invasion and lead to interventions that can potentially enhance placental development.

Angiogenesis (new blood vessel formation)

During human pregnancy, the placenta develops through a process of vasculogenesis and angiogenesis which when complete allows for the efficient exchange of nutrients, gas and waste products between the fetus and the mother. Adequate maternal blood flow to the placenta is essential for normal fetal growth and development.

A significant reduction of blood flow is observed in intrauterine growth restriction (IUGR), which affects 4-7 % of all pregnancies. Pre-eclampsia is a condition characterised by maternal hypertension and proteinuria, which often occurs concurrently with IUGR. IUGR is typically diagnosed by ultrasound from 26 weeks onwards and babies are delivered up to 12 weeks early necessary to prevent fetal demise.

There are significant long term complications of pre-term delivery, where affected individuals are at increased risk of hypertension, diabetes and cardiovascular disease later in life.

Studies have shown that the placenta seen in IUGR pregnancies is poorly vascularised and cannot meet the requirements of the developing fetus. This incomplete placental development is associated with lower serum levels of Angiopoitein-2 (Ang-2) a substance known to be involved in angiogenesis, in the first trimester of pregnancies which later developed IUGR, compared to normal pregnancies. This finding may lead to the development of a first trimester screening test capable of identifying those pregnancies at increased risk of IUGR.

Studies are currently being pursued to elucidate potential mechanisms involved in the development of IUGR pregnancies. These studies are focused on three main areas:

• Regulation and production of the family of Angiopoietins, their receptors, and their biological action in cells involved in human reproduction, using primary cell culture models.
• Hypoxia is thought to be important in the early stages of placental neo-genesis. Investigations are currently being undertaken assessing the action and regulation of Angiopoietins and their receptors under hypoxic conditions in endothelial and trophoblasts cells.
• The development of a study aimed at establishing a correlation between maternal serum levels of Ang-2 in early pregnancy and adverse pregnancy outcomes later in pregnancy, using a novel investigative approach utilising routinely collected health data