This study is aimed to examine the association between umbilical cord blood (UCB) derived exosomal microRNA (miRNA) with preeclampsia (PE) and to further explore the mechanism of a key differential gene (hsa-miR-125a-5p) in preeclampsia. Umbilical cord blood exosomal miRNA(exo-miRNA) from normal pregnant women and pregnant women with preeclampsia was processed via miRNA sequencing. Quantitative real-time polymerase chain reaction (QRT-PCR) was performed to assess the expression of miR-125a-5p in normal and PE placental tissues and peripheral blood derived exosomes in the third trimester. Human trophoblast cell line HTR8/SVneo was assigned as the negative control and miR-125a5p mimics. QRT-PCR and Western blot were performed to identify the expressions of miR-125a-5p and vascular endothelial growth factor A (VEGFA). CCK8, flow cytometry, wound-healing and Transwell assays were used to analyze the effect of miR-125a-5p on HTR8/SVneo cell migration, proliferation, and cycle distribution. Tube formation was performed to estimate the angiogenesis ability of miR-125a-5p on HUVECs. In conclusion, miR-125a-5p expression in PE placental tissues was higher than in normal subjects, while the expression of VEGFA was lower in PE placental tissues. We then compared the miR-125a-5p mimics group with the negative control group and found that in the mimics group, the cell migration, proliferation and angiogenesis abilities were decreased, and more cells were arrested in the S stage. Our study systematically profiled the UCB exo-miRNA in normal and PE pregnant women and demonstrated that dysregulation of miR-125a-5p might affect HTR8/SVneo cell proliferation and migration and inhibit angiogenesis by regulating VEGFA, indicating that miR-125a-5p is involved in the progression of PE. (C) 2020 The Authors. Published by Elsevier Inc.