Volume electron microscopy reveals placental ultrastructure in 3D

Many structures necessary for placental function can only be visualised at the ultrastructural scale. Recent technological advances have made Volume electron microscopy (volume EM) approaches much more accessible. Volume EM allows the ultrastructure of tissues, cells and organelles to be visualised in 3D. It also allows the 3D spatial relationships between these structures to be determined. This review will highlight the potential for volume EM to advance our understanding of placental ultrastructure. It will focus on the human term placenta highlighting key findings spanning the placental barrier from trans-syncytial nanopores in the syncytiotrophoblast to tunnelling nanotubes in the fetal capillary endothelium. Volume EM is advancing our understanding of placental ultrastructure, but to fully exploit its potential, it will be necessary to use it as part of multimodal and correlative workflows. The complementary strengths of these different approaches can complement volume EM and reveal the biological significance of its novel observations. The use of volume EM also highlighted how ultrastructural features might underpin pregnancy pathologies and demonstrates the need for more research in this underrepresented area.