Lower level of miR-34a leads to placenta accreta spectrum by promoting the proliferation, migration of trophoblast villous epithelial cells and enhanced the angiogenesis of vascular endothelial cells.

Abstract

Introduction: The overall prevalence of placenta accreta spectrum (PAS) is approximately 0.17 %, but it accounts for 7 % of maternal mortality and is associated with intraoperative and postoperative morbidity. The pathogenesis mechanisms of PAS include an imbalance between decidualization and trophoblast invasion. The aim of this study is to identify the pathogenesis roles of miR-34a in PAS.

Methods: For this purpose, we collected 15 placenta tissues from pregnant subjects with PAS complications and another 15 placenta tissues from normal pregnancy (NP) cases. Then, we conducted in situ hybridization assay to compare miR-34a expression level, followed by in vitro simulations of NP and PAS with miR-34a and scrambled control (SC) mimic transfection in cells, respectively. Next, we conducted in vitro cellular assays to investigate the pathogenesis mechanisms of miR-34a in PAS.

Results: We first confirmed significantly lower level of miR-34a in the trophoblast villous (TV) from PAS patients. By in vitro assays, lower miR-34a led to significantly higher cell proliferation and enhanced cell migration in TV epithelial cells. In addition, lower miR-34a resulted in elevated angiogenesis ability in vascular endothelial cells. Finally, to identify the pathway involved by miR-34a in PAS, we used microarray (raw data available via NCBI GEO database with accession number GSE279257) and flow cytometry to confirm that lower miR-34a significantly repressed the apoptosis activity in TV epithelial cells.

Discussion: In this study, we not only confirmed miR-34a as a biomarker of PAS but also clarified the in vitro pathogenesis mechanism of miR-34a in PAS.