Mapping the maternal-fetal interface at a single-cell resolution to interrogate the aetiology of severe pre-eclampsia and identify potential disease

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During pregnancy there is a highly coordinated dialogue between mother and fetus and this communication, once established, ensures the correct development of the baby and allows the mother to both tolerate her unborn child, and remain well. A common and dangerous pregnancy complication is pre-eclampsia (PE), where a pregnant woman develops high blood pressure that can lead to organ failure. Unfortunately, there is no treatment available and the underlying cause of this condition remains unknown. Recent research by others and us suggests dysregulation of the immune response at the mother-fetal interface, which affects how fetal tissues connect to the maternal blood system. We therefore aim to study cell dialogue at the interface of the mother and her unborn child 'the fetus' known as the maternal-fetal interface (MFI). The MFI consists of different tissues belonging to both mother and fetus and includes; the maternal uterine 'womb' wall, the placenta, which supplies the fetus, along with the membrane that covers the wall of the womb and placenta. We will use technologies that allow us to interrogate the cells in these tissues at a single cell resolution, identifying both the specific cell type that are present, as well as what it is making or signalling. These approaches allow the quantification of the expression of thousands of genes in their native 'original' context.The comparison between patients with severe PE (which poses the greatest clinical burden including maternal and fetal death and disability) versus healthy controls will help us detect specific genes expressed differently in the pathological condition. The groups will enable us to understand the differences seen and how gestational age affects these changes. With this information, we will look for these markers in maternal blood samples, aiming to develop a new way to diagnose PE, that reveals what is the cause of the disease. This approach lends itself to a more personalised form of treatment. Our research may contribute to finding a treatment for this severe pregnancy complication as well as investigating whether its presence can be identified through a more simple blood test.