905: Release of placental exosomes is reduced in spontaneous preterm births

Abstract

Feto-maternal signaling is considered to contribute to the timing of birth. Exosomes originating from the placenta may transport signals to maternal tissues where they deposit protein and RNA cargo into target cells. Our previous results indicate that tissues including the placenta secrete lower levels of exosomes into blood under pathological conditions. We hypothesize that differential secretion of placental exosomes and expression of exosome contents will reflect the underlying physiology of spontaneous preterm birth (SPTB). We performed a case-control study comparing levels of placental exosomes in maternal plasma samples obtained following hospital admission from SPTB cases to term delivery and medically-indicated preterm delivery (MPTB)controls. Exosomes were isolated by ultracentrifugation, and nanoparticle analysis was performed to demonstrate that the majority of isolated microvesicles were in the size range consistent with exosomes. Western blots were performed utilizing antibodies against syncytin-1, a placenta-specific protein, and levels of placental exosomes were normalized to TSG-101 (an exosome marker) levels in the plasma samples (Figure 1). Levels of placental exosomes were measured in 16 SPTB cases (20-34 weeks), 10 MPTB (20-34 weeks), and 16 uncomplicated term delivery controls (38-39 weeks). Nanoparticle detection and electron microscopy showed that intact exosomes (range 40–100 nm) were enriched. Relative levels of placental exosomes (syncytin-1 label normalized to TSG 101) were similar in term delivery controls (established at 1.000) and MPTB (1.174+0.626) but were significantly lower in SPTB cases (0.493+0.205, P=0.036, Figure 2). Shedding of placental exosomes into maternal blood was lower in SPTB cases compared to term delivery and MPTB controls. It will be important to compare maternal plasma exosome levels earlier in pregnancy and the proteomic and RNA signatures in SPTB cases and term delivery controls. These studies have the potential to identify novel pathways by which the fetus contributes to the timing of birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)