Exosome enriched leucine-rich alpha-2-glycoprotein-1 and extracellular matrix protein 1 proteins induce abnormal placental angiogenesis in pregnant mice

Gestational Diabetes Mellitus (GDM) is characterized by a high risk of fetal macrosomia and placenta hypervascularization. Exosomes has been known participating in various physiological and pathological processes, including pro-angiogenic function. However, the effects of umbilical cord blood derived exosomes from cases of GDM (GDM-exo) on placental vascular network formation remain unclear.In the current study, we isolated and identified exosomes in umbilical cord blood from both normal (N-exo) and GDM pregnancies. Meanwhile, we investigated the effects of umbilical cord blood derived exosomes on placental angiogenesis both in vitro and in vivo.Our data indicated that in a mouse model, the placenta and fetus weight were significantly higher in the ones administrated with GDM-exo when compared with N-exo. Meanwhile, GDM-exo significantly enhanced placental endothelial cells functions in both HUVEC and HPMEC endothelial cell models. Importantly, we explored two up-regulated proteins in GDM-exo, namely leucine-rich alpha-2-glycoprotein-1 (LRG1) and extracellular matrix protein 1 (ECM1) by proteome analysis, which performed largely pro-angiogenic function and probably resulted in hypervascularization in GDM placenta.Thus, we proposed that abundant LRG1 and ECM1 enriched GDM-exo may take important roles in regulating pathological placental angiogenesis.