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Antiphospholipid antibodies (aPL) are autoantibodies that target phospholipid‐binding proteins, such as β2 glycoprotein I (β2GPI), and can induce thrombosis systemically, as well as increase the risk of obstetric complications such as recurrent miscarriage and preeclampsia. Due to the expression of β2GPI by placental trophoblasts, aPL readily target the maternal‐fetal interface during pregnancy and many studies have investigated the deleterious effects of aPL on placental trophoblast function. This review will focus on studies that have examined the effects of aPL on the production and modification of extracellular vesicles (EVs) from trophoblasts, as EVs are a key mode of feto‐maternal communication in both normal and pathological pregnancy. A more comprehensive understanding of the effects of aPL on the quantity and cargo of EVs extruded by the human placenta may contribute to our current knowledge of how aPL induce both systemic and obstetric disease.

Placental extracellular vesicles (EVs) have increasingly been recognized as a major mediator of feto-maternal communication. However, the cellular and molecular mechanisms of the uptake of placental EVs by recipient cells are still not well-understood. We previously reported that placental EVs target a limited number of organs in vivo. In the current study, we investigated the mechanisms underlying the uptake of placental EVs into target cells. Placental EVs were derived from explant cultures of normal or preeclamptic placentae. The mechanisms underlying the uptake of placental EVs were elucidated, using the phagocytosis or endocytosis inhibitor, trypsin-treatment or integrin-blocking peptides. The endothelial cell activation was studied using the monocyte adhesion assay after the preeclamptic EVs exposure, with and/or without treatment with the integrin blocking peptide, YIGSR. The cellular mechanism of the uptake of the placental EVs was time, concentration and energy-dependent and both the phagocytosis and endocytosis were involved in this process. Additionally, proteins on the surface of the placental EVs, including integrins, were involved in the EV uptake process. Furthermore, inhibiting the uptake of preeclamptic EVs with YIGSR, reduced the endothelial cell activation. The interaction between the placental EVs and the recipient cells is mediated by integrins, and the cellular uptake is mediated by a combination of both phagocytosis and endocytosis.

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