PE is a frequently-occurring disorder associated with pregnancy and may produce detrimental maternal and neonatal consequences affecting almost 3–5% of total pregnancies [1,2]. It can induce hypertension and proteinuria, and is one of the most common causes for maternal morbidity [3]. The primary pathological symptom for early-phase PE is characterized by an aberrant placenta development. It has now been commonly recognized that the pathogenesis of PE is triggered by insufficient trophoblast invasion during the early pregnancy, contributing to oxidative stress elevation and subsequent progression of systemic endothelial disorder, ultimately resulting in clinical symptoms of PE [[4], [5], [6], [7]]. Therefore, identifying the factor that could affect the invasion capability of trophoblasts is critical for better understanding the mechanism behind PE pathogenesis.

Non-coding RNA is a class of RNA not participating in encoding proteins, and miRNA is a type of small single‐stranded non-coding RNA, usually consisting of ∼22 nucleotides [8,9]. Several studies have indicated differential expressions of miRNAs in pregnant PE patients, and reported that miR-136, miR-23a and some other novel miRNAs are significantly enriched in placentas; dysregulation of miRNAs has also been observed in hypoxic stress and other syndromes [10,11].

Decidual stromal cells are the main type of resident mesenchymal cells at the fetal-maternal interface with fibroblasts-like shape, accounting for 40% of total cells. It has been well-documented that decidual stromal cells participate in regulating blastocyst implantation, modulating trophoblast invasion, and maintaining oxidative stress resistance, tissue hemostasis, immune responses at the fetal-maternal interface, and their decidualization through autocrine and paracrine effects [[12], [13], [14]]. Macrophage is another critical component in the first-trimester decidua, and it has been reported that an excess of macrophages infiltration seems to be correlated with reduced trophoblast invasion [[15], [16], [17], [18]].

In this study, bioinformatics study was used to analyze differential miRNA expression in decidual stromal cells from PE patients and healthy donors. The result indicated that miR-455–3p expression was downregulated in decidual stromal cells from PE patients. Decidual stromal cells were transfected by miR-455–3p inhibitors to investigate its effect. After transfection, cytokine secretion was significantly increased. And luciferase activity assay confirmed that the NFAT5 mRNA was the direct target of miR-455–3p; an overexpression of NFAT5 could promote cytokine secretion. We also studied the effect of decidual stromal cells-derived CM. After treatment with decidual stromal cells-derived CM, significantly M1 polarization was observed in macrophages. Transwell invasion assay indicated that M1 polarized macrophages subsequently suppress the invasion capability of trophoblast.

Taken together, our result indicated that downregulation of miR-455–3p in decidual stromal cells promotes macrophages polarization and suppresses trophoblast invasion.