Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Excessive M1 macrophage was found to be involved in RSA, but the underlying mechanisms remains unclear. MicroRNAs play critical roles in RSA as well as the polarization of macrophages; however, the regulatory effect of miRNAs on M1 differentiation in RSA has not been fully investigated. In this study, miRNA microarray assay revealed that miR-103 was significantly decreased in RAW264.7-derived M1 macrophages upon IFNγ and LPS stimulation. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that in RSA patients, miR-103 expression was decreased substantially, and negatively correlated with that of STAT1. Moreover, down-regulation of miR-103 could sensitively discriminate RSA patients from normal pregnancies (NP) subjects. Experiments in vitro showed that overexpression of miR-103 suppressed M1 polarization by inhibiting STAT1/IRF1 signaling pathway and vice versa. miR-103 regulated STAT1 expression by direct binding to its 3'-UTR. Moreover, our in vivo study demonstrated that overexpressed miR-103 could reduce mice embryo resorption and M1 polarization effectively. Overall, the results suggested that decreased miR-103 was involved in RSA by increasing M1 macrophage polarization via promoting STAT1/IRF1 signaling pathway. miR-103 may be explored as a promising diagnostic marker and therapeutic target for RSA.

中文翻译：

---

MiR-103 通过抑制 STAT1 介导的 M1 巨噬细胞极化来防止复发性自然流产。

复发性自然流产 (RSA) 是早期妊娠的常见并发症。发现过多的 M1 巨噬细胞参与了 RSA，但其潜在机制尚不清楚。MicroRNA 在 RSA 以及巨噬细胞的极化中起着关键作用；然而，miRNAs对RSA M1分化的调节作用尚未得到充分研究。在这项研究中，miRNA 微阵列分析显示 RAW264.7 衍生的 M1 巨噬细胞中 miR-103 在 IFNγ 和 LPS 刺激下显着降低。定量实时聚合酶链反应（qRT-PCR）分析显示，在 RSA 患者中，miR-103 表达显着降低，且与 STAT1 呈负相关。此外，miR-103 的下调可以敏感地区分 RSA 患者与正常妊娠 (NP) 受试者。体外实验表明miR-103的过表达通过抑制STAT1/IRF1信号通路抑制M1极化，反之亦然。miR-103 通过直接结合其 3'-UTR 来调节 STAT1 的表达。此外，我们的体内研究表明，过表达的 miR-103 可以有效减少小鼠胚胎吸收和 M1 极化。总体而言，结果表明，通过促进 STAT1/IRF1 信号通路增加 M1 巨噬细胞极化，减少的 miR-103 参与了 RSA。miR-103 可以作为 RSA 有前景的诊断标志物和治疗靶点进行探索。我们的体内研究表明，过表达的 miR-103 可以有效减少小鼠胚胎吸收和 M1 极化。总体而言，结果表明，通过促进 STAT1/IRF1 信号通路增加 M1 巨噬细胞极化，减少的 miR-103 参与了 RSA。miR-103 可以作为 RSA 有前景的诊断标志物和治疗靶点进行探索。我们的体内研究表明，过表达的 miR-103 可以有效减少小鼠胚胎吸收和 M1 极化。总体而言，结果表明，通过促进 STAT1/IRF1 信号通路增加 M1 巨噬细胞极化，减少的 miR-103 参与了 RSA。miR-103 可以作为 RSA 有前景的诊断标志物和治疗靶点进行探索。