The placenta is composed of syncytiotrophoblasts (STBs) and their progenitors: cytotrophoblasts (CTBs). Differentiated CTBs also invade the decidual lining of the uterus where they remodel the maternal vascular network. Extracellular vesicles (EVs) have been proposed as a form of communication between the embryo/foetus and the mother to precisely regulate uterine functions, including inflammation, during such processes; however, most studies have focused on exosomes derived from STBs. Now, Susan Fisher and colleagues profile exosomes produced by second-trimester human CTBs, isolated by ultracentrifugation. Using transmission electron microscopy and immunoblotting, the researchers identify a population of cup-shaped, exosome-like EVs in the 100,000 g fraction that express exosomal and placental markers, such as CD9 and HLA-G, respectively. Next, they profiled the proteome using mass spectrometry and a cytokine array, and found high levels of tumour necrosis factor α (TNFα) are associated with these EVs. CTB EVs increased the secretion of NF-κB targets (such as IL8) from the decidua, whereas a soluble form of the TNFα receptor inhibited this ability. Together, this work provides global characterisation of CTB EVs – an important library for future studies – and indicates that CTB EVs promote the release of inflammatory cytokines from the decidua.
