Transfer of miR-15a-5p by placental exosomes promotes pre-eclampsia progression by regulating PI3K/AKT signaling pathway via CDK1.

Preeclampsia (PE) is a systemic complication that occurs after the 20th week of gestation and is characterized by the onset of hypertension and proteinuria. Dysregulated circulating microRNA (miRNA) has usually been noted in PE. Understanding the release profile and bioactivity of placental exosomes is a promising mode of identifying dysregulated miRNA, which may be useful biomarkers of PE. Herein, we aimed to investigate the role of placental exosomes and their miRNA cargo miR-15a-5p in PE. miR-15a-5p was found upregulated in exosomes isolated from maternal plasma of PE pregnant women as compared to those from normal pregnant women. Placental exosomes derived from PE pregnant women suppressed the proliferation and invasion of HTR-8/SVneo cells but promoted cell apoptosis, which was dictated by their cargo miR-15a-5p. Further investigation showed that exosomal miR-15a-5p inhibited the activation of the PI3K/AKT pathway by down-regulating CDK1, thus suppressing HTR-8/SVneo cell proliferation, invasion, and apoptosis. In vivo analysis demonstrated that placental exosomes treated with miR-15a-5p inhibitor attenuated histopathologic changes and apoptosis in the placenta of PE mice. In conclusion, these results provided evidence that transfer of miR-15a-5p by placental exosomes could be a promising therapeutic target to combat PE.