Syncytiotrophoblast derived extracellular vesicles in relation to pre-eclampsia

The syncytiotrophoblast, a fused single-cell layer between mother and fetus, constitutively releases extracellular vesicles (STBEV) directly into the maternal circulation. STBEV contain a variety of proteins and RNA which can be targeted to specific cells. In pre-eclampsia, asymptomatic placental oxidative stress is a precursor to later multi-organ dysfunction in the mother. Increased STBEV release in pre-eclampsiasia is considered a manifestation of syncytiotrophoblast stress, which may play a key role in signaling between fetus and mother. STBEV release in pre-eclampsia changes, both in terms of volume and content. In this review, we outline the latest advances in STBEV isolation and detection. We consider evidence for differential STBEV release, protein cargo and RNA content in pre-eclampsia, highlighting common pitfalls in study design. We summarise studies to date demonstrating STBEV actions on target cells. Ultimately, we consider how STBEV fit into the pathophysiology of the heterogeneous syndrome of pre-eclampsia. The key unifying concept in early- and late-onset pre-eclampsia is syncytiotrophoblast stress. We submit that STBEV are the key stress signal in pre-eclampsia. We believe that further investigation of STBEV release, content, and actions may offer valuable insights into pre-eclampsia pathophysiology and potential new clinical diagnostics and therapeutic targets.