Strategies for investigating the maternal-fetal interface in the first trimester of pregnancy: What can we learn about pathology?

The pathologies of the pregnancy complications pre-eclampsia (PE) and fetal growth restriction (FGR) are established in the first trimester of human pregnancy. In a normal pregnancy, decidual spiral arteries are transformed into wide diameter, non-vasoactive vessels capable of meeting the increased demands of the developing fetus for nutrients and oxygen. Disruption of this transformation is associated with PE and FGR. Very little is known of how these first trimester changes are regulated normally and even less is known about how they are compromised in complicated pregnancies. Interactions between maternal and placental cells are essential for pregnancy to progress and this review will summarise the challenges in investigating this area. We will discuss how first trimester studies of pregnancies with an increased risk of developing PE/FGR have started to provide valuable information about pregnancy at this most dynamic and crucial time. We will discuss where there is scope to progress these studies further by refining the ability to identify compromised pregnancies at an early stage, by integrating information from many cell types from the same pregnancy, and by improving our methods for modelling the maternal-fetal interface in vitro.