LAUSR

Background Extracellular vesicles (EVs) are communicating physio/pathological signals between organs. In preeclampsia (PE) – a life threatening pregnancy complication - there is an elevated shedding of EVs by the placental syncytiotrophoblast (STB-EVs) into the maternal circulation. Different STB-EVs subtypes carries each a large repertoire of proteins and RNAs to signal the maternal organs. Here we set to determine placental protein 13 (PP13) to identify if it is included in the STB-EVs’ cargo, whether it is located inside or outside, and if and how it change in PE given that maternal serum PP13 is reduced during the first trimester in patients who subsequently developed PE. Furthermore, PP13 causes expansion of the maternal uterine arteries to accommodate the increase blood flow in pregnancy, induces apoptosis of lymphocytes and enhances cytokines secretion related to immune functions. Methods Placentae were obtained at caesarean section deliveries of 20 PE and 19 controls. The STB-EVs were collected from the maternal side perfusate by the dual placental lobe perfusion, sequential centrifugation and filtration. Three population subtypes were isolated: STB microvesicles (STB-MVs), STB-Exosomes (STB-EXs) and total STB-EVs. Placental origin was assessed by Western blot and size distribution by Nanoparticle Tracking Analysis. PP13 was quantified by ELISA. Results All STB-EVs preparation had placental alkaline phosphatase (PLAP) biomarker. ALIX and CD9 were exclusively expressed in STB-EXs. PP13 was determined for the first time in all three STB-EVs preparations, and was expressed in both their inside and their surface. PP13 was significantly lower in PE compared to control in the total STB-EVs and STB-MVs, but not in STB-EXs. Conclusion At delivery there is a decreased in PP13 levels in STB-EVs derived from PE. Circulating PP13 is therefore either soluble or associated with STB-EVs, and each may deliver distinct PE associated signals. Funding MS was sponsored by Daniel Turnberg Fellowship, UK.