Abstract

The ability to directly monitor the status of the placenta throughout pregnancy would be a major advance in both general and personalized obstetric care, allowing treatments to be tailored to the dynamic changes that can occur in gestation. Syncytiotrophoblast extracellular vesicles (STBEV) are membrane bound vesicles, released from the surface of the placenta directly into the maternal circulation, in the form of exosomes, microvesicles and apoptotic bodies. They carry many syncytiotrophoblast derived factors such as proteins, lipids, glycans and nucleic acids, which together could dynamically signal to the mother the status of the placenta. We review STBEV research and discuss the potential for STBEV to be used as circulating syncytiotrophoblast biopsies, accessible via a simple blood sample throughout pregnancy, giving a real-time readout of syncytiotrophoblast health. We also highlight advances in the use of extracellular vesicles as circulating tumour derived biopsies in the field of cancer research, which could prove beneficial to obstetric care.

Highlights

  • The syncytiotrophoblast (STB) is fundamental to the establishment and maintenance of a healthy pregnancy

  • We have found placental alkaline phosphatase (PLAP) expression to be significantly lower for PE-Syncytiotrophoblast extracellular vesicles (STBEV), compared to those derived from healthy pregnancy placentas, using mass spectrometry (measures total PLAP; D Tannetta unpublished observation), Western blotting and flow cytometry, suggesting that PLAP positivity may give an underestimate of STBEV number in PE [21]

  • Most focus has been on STBEV as biomarkers to predict or diagnose PE, with the cargo giving a PE ‘finger print’ reflecting specific pathological mechanisms such as inflammatory, oxidative and ER stresses

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Summary

Introduction

The syncytiotrophoblast (STB) is fundamental to the establishment and maintenance of a healthy pregnancy. Acute or chronic changes that occur through physiological or pathological mechanisms can lead to impaired STB function. Such changes will probably vary within one placenta and between individual pregnancies, certain pathological processes may be common to specific complications [2]. Regulation and cell maintenance, and as a consequence of pathologies, such as cancer, cardiovascular disease and inflammatory disorders [3e5]. Cellular responses such as activation, stress and death alter the molecular fingerprint of the EV cargo, making them potential biopsies of inaccessible tissues and allowing measurement of multiple biomarkers derived from a specific source [6]. STB releases EV (STBEV), containing a complex cargo of RNAs, proteins, glycans and lipids, from the apical surface directly into the maternal circulation in normal pregnancy and PE, fuelling interest in their use as biomarkers of placental wellbeing [7e12]

Types of STBEV and their role in normal pregnancy and PE
STBEV as STB biopsies
Isolation of circulating STBEV
Parallels with cancer EV
Conclusions

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