Spontaneous abortion (SA) is a common pregnancy failure, but the cause of numerous cases remains unexplained. Decidual immune cells (DICs)-mediated cytokine microenvironment is involved in pregnancy and regulated by many microRNAs, but whether microRNA-146a-5p (miR-146a) regulate the decidual cytokine microenvironment and the potential mechanisms in unexplained SA pathogenesis have rarely been reported. In this study, the levels of cytokines and miR-146a in healthy and unexplained SA deciduae were first investigated, and the correlation between them was analyzed. Then, the effect of miR-146a inhibitor on cytokines was assessed in healthy deciduae-derived DICs. Third, the downstream targets and related molecular mechanisms of miR-146a were analyzed by bioinformatics, and the levels of the predicted targets in deciduae were assessed, followed by the correlation analysis between the levels of miR-146a and the targets. Finally, the effect of miR-146a on the predicted targets and inflammatory cytokines was validated in unexplained SA deciduae-derived DICs. As a result, decreased miR-146a correlated with the cytokine disorder in unexplained SA deciduae, and inhibition of miR-146a promoted pro-inflammatory response in healthy deciduae-derived DICs. One hundred four target genes and related molecular mechanisms of miR-146a were predicted, among which the toll-like receptor (TLR) pathway might be associated with the decidual cytokine regulation. Upregulation of miR-146a inhibited the expression of the predicted molecules enriched in the TLR pathway and improved the cytokine disorder in unexplained SA deciduae-derived DICs. Collectively, miR-146a improves the decidual cytokine microenvironment by regulating the TLR pathway in unexplained SA, providing novel potential targets for further therapeutic research.

自发流产（SA）是常见的妊娠失败，但是许多病例的原因仍无法解释。蜕膜免疫细胞（DICs）介导的细胞因子微环境参与妊娠并受许多microRNA调控，但是很少报道microRNA-146a-5p（miR-146a）是否调节蜕膜细胞因子微环境以及无法解释的SA发病机制的潜在机制。在这项研究中，首先调查了健康和无法解释的SA十足虫中细胞因子和miR-146a的水平，并分析了它们之间的相关性。然后，在健康的蜕皮动物来源的DIC中评估了miR-146a抑制剂对细胞因子的作用。第三，通过生物信息学分析了miR-146a的下游靶标和相关分子机制，并评估了十足动物中预测靶标的水平，然后进行miR-146a水平与靶标之间的相关性分析。最后，miR-146a对预测的靶标和炎性细胞因子的作用已在无法解释的SA十足菌来源的DIC中得到验证。结果，减少的miR-146a与无法解释的SA十足中的细胞因子紊乱相关，而抑制miR-146a可以促进健康的十足中DICs的促炎反应。预测了miR-146a的104个靶基因及其相关的分子机制，其中toll样受体（TLR）途径可能与蜕膜细胞因子的调控有关。miR-146a的上调抑制了富含TLR途径的预测分子的表达，并改善了来自无法解释的SA衍生的DICs中细胞因子的紊乱。总的来说，