Background Fetal cell-derived exosomes (extracellular vesicles, 40–160 nm) are communication channels that can signal parturition by inducing inflammatory changes in maternal decidua and myometrium. Little is known about maternal cell-derived exosomes and their functional roles on the fetal side. This study isolated and characterized exosomes from decidual and myometrial cells grown under normal and inflammatory/oxidative stress conditions and determined their impact on fetal membrane cells. Methods Decidual and myometrial cells were grown under standard culture conditions (control) or exposed for 48 h to cigarette smoke extract or tumor necrosis factor-α, as proxies for oxidative stress and inflammation, respectively. Exosomes were isolated from media (differential ultra-centrifugation followed by size exclusion chromatography), quantified (nano particle tracking analysis), and characterized in terms of their size and morphology (cryo-electron microscopy), markers (dot blot), and cargo contents (proteomics followed by bioinformatics analysis). Maternal exosomes (109/mL) were used to treat amnion epithelial cells and chorion trophoblast cells for 24 h. The exosome uptake by fetal cells (confocal microscopy) and the cytokine response (enzyme-linked immunosorbent assays for IL-6, IL-10, and TNF-α) was determined. Results Exosomes from both decidual and myometrial cells were round and expressed tetraspanins and endosomal sorting complexes required for transport (ESCRT) protein markers. The size and quantity was not different between control and treated cell exosomes. Proteomic analysis identified several common proteins in exosomes, as well as unique proteins based on cell type and treatment. Compared to control exosomes, pro-inflammatory cytokine release was higher in both amnion epithelial cell and chorion trophoblast cell media when the cells had been exposed to exosomes from decidual or myometrial cells treated with either cigarette smoke extract or tumor necrosis factor-α. In chorion trophoblast cells, anti-inflammatory IL-10 was increased by exosomes from both decidual and myometrial cells. Conclusion Various pathophysiological conditions cause maternal exosomes to carry inflammatory mediators that can result in cell type dependent fetal inflammatory response.

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INTRODUCTION: To compare maternal and neonatal outcomes between elective induction (EIOL) and expectant management (EM) in low risk women with a prior cesarean delivery. METHODS: Records of women with a prior cesarean and whose plan of delivery was a trial of labor (TOLAC) were reviewed. Patients who reached 39 weeks and were low risk were included and divided into 2 groups. Those who were induced electively between 39 weeks 0 days and 39 weeks 6 days (EIOL) versus those who were not (EM). Low risk was defined as absence of a maternal or fetal indication for delivery prior to 41 weeks 6 days. The primary outcome was a composite of adverse neonatal outcomes. Secondary outcomes included repeat cesarean delivery (CD) and maternal morbidities. RESULTS: From July 2014–July 2019, 552 low risk women underwent TOLAC: 317 women in the EM and 235 in the EIOL group. The primary outcome occurred in 5.38% in the EM group and 3.40% in the EIOL group (OR 0.62, 95% CI 0.23–1.55). The frequency of CD was 31.86% in the EM group and 26.38% in the EIOL group (OR 0.766, 95% CI 0.52–1.13). CONCLUSION: Elective induction of labor at 39 weeks among low risk women with a history of prior cesarean section was not associated with an increase in perinatal morbidity, and was associated with lower rates of hysterotomy-associated complications and medically-indicated delivery. It is reasonable to offer elective induction of labor at 39 weeks to women who are candidate for TOLAC.

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