Background Preeclampsia is a unique multisystem disorder that affects 5–8% of pregnancies. A high level of soluble fms-like tyrosine kinase-1 (sFlt-1) is a hallmark of preeclampsia that causes endothelial dysfunction. Exosomes derived from mesenchymal stem cells (MSCs) have been indicated to improve endothelial performances by transporting signals to target cells. We hypothesized that exosomes derived from MSCs have potential effects against preeclampsia. Methods We collected human umbilical cord MSC-derived exosomes (HUCMSC-exos) by ultracentrifugation. The size and morphology of the exosomes were examined using a transmission electron microscope and nanoparticle tracking analysis. Pregnant mice were injected with murine sFlt-1 adenovirus to build the preeclampsia-like mouse model and then treated with HUCMSC-exos. Human umbilical vein endothelial cells (HUVECs) were infected with lentiviruses expressing tet-on-sFlt-1 to obtain cells overexpressing sFlt-1. Cell proliferation and migration assays were used to measure the endothelial functions. The exosomes enriched proteins underlying mechanisms were explored by proteomic analysis. Results In the current study, we successfully collected the cup-shaped HUCMSC-exos with diameters of 30–150 nm. In the sFlt-1-induced preeclampsia mouse model, HUCMSC-exos exhibited beneficial effects on adverse birth events by decreasing blood pressure and improving fetal birth weight. In addition, preeclamptic dams that were injected with HUCMSC-exos had rebuilt dense placental vascular networks. Furthermore, we observed that HUCMSC-exos partially rescued sFlt-1-induced HUVECs dysfunction in vitro. Proteomics analysis of HUCMSC-exos displayed functional enrichment in biological processes related to vesicle-mediated transport, cell communication, cell migration, and angiogenesis. Conclusion We propose that exosomes derived from HUCMSCs contain abundant Versican and play beneficial roles in the birth outcomes of sFlt-1-induced preeclamptic mice by promoting angiogenesis. Graphical Abstract

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Purpose Infants with macrosomia are more likely to be born to mothers with gestational diabetes mellitus (GDM). This study aimed to investigate the associations between maternal blood glucose levels and fetal weight, placental weight, and risk of macrosomia in mothers with GDM. Patients and Methods This retrospective study included 3211 singletons of mothers with GDM at the Shanghai First Maternity and Infant Hospital between January 2017 and December 2019. All women underwent an oral glucose tolerance test (OGTT) during the 24–28 weeks gestation period. Data on fetal and placental parameters were collected at delivery. Multiple linear regression models were used to evaluate the associations of maternal blood glucose levels with fetal weight and placental weight, while multiple logistic regression model was used to estimate the association between maternal blood glucose levels and the risk of macrosomia. Results The prevalence of GDM in our study was 7%. Fasting plasma glucose (FPG) was positively correlated with fetal weight (r 2 =0.0329, P<0.001), and macrosomia risk (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.93–3.04; P<0.001). After adjusting for gestational age, the result remained significant (OR, 2.67; 95% CI, 2.11–3.38; P<0.001). In contrast, there was no significant relationship between 1-h plasma glucose (1hPG) or 2-h plasma glucose (2hPG) and fetal weight (P=0.18, P=0.46). Additionally, 1hPG or 2hPG was not strongly associated with macrosomia risk (OR, 0.95; 95% CI, 0.85–1.05; P=0.32 vs OR, 0.94; 95% CI, 0.85–1.05; P=0.28). Maternal blood glucose levels did not affect placental weight. The associations were similar in women carrying male and female fetuses. Conclusion Maternal fasting plasma glucose levels were strongly associated with increased birth weight and macrosomia risk. Our findings suggest that fasting plasma glucose may predict birth weight.

Aim: Exosomes have emerged as important regulators in the communication between maternal peripheral blood and placenta. We aimed to compare maternal plasma exosomal miRNAs profile between healthy pregnant and nonpregnant women, screen for differential expressed miRNAs and their potential regulatory role during pregnancy. Methods: We isolated exosomes from plasma of mid-trimester, last trimester, and nonpregnant women (n = 6 each group), analyzed the miRNA profile using next-generation sequencing. Results: Several miRNA clusters were expressed in plasma exosomes, such as C19MC, C14MC, and let-7 family, miRNAs in each cluster may have synergistic effect during pregnancy. We assumed maternal circulating exosomal miRNA could be transported into placenta or selectively uptook by placenta, which was consistent with the fact that many pregnancy-associated or placenta highly expressed miRNAs reduced in exosomes during pregnancy. Some exosomal miRNAs were mainly secreted by the placenta, which could act as markers that reflect changes in the function and microenvironment of the placenta. Conclusions: Exosomal miRNAs are associated with placenta development and have potential as molecular markers.

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