To date, the microRNA (miRNA) expression profile of plasma exosomes in women whose pregnancy is complicated by gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small RNA sequencing in 12 GDM and 12 normal glucose tolerance (NGT) pregnant women and validated in 102 GDM and 101 NGT pregnant women. A total of 22 exosomal miRNAs were found and five of them were verified by qRT-PCR. Exosmal miR-423-5p was upregulated, while miR-122-5p, miR-148a-3p, miR-192-5p, and miR-99a-5p were downregulated in women whose pregnancy is complicated by GDM. IGF1R and GYS1 as target genes of miR-423-5p, and G6PC3 and FDFT1 as target genes of miR-122-5p, were associated with insulin and AMPK signaling pathways and may participate in the regulation of metabolism in GDM. The five exosomal miRNAs showed an AUC of 0.82 (95%CI, 0.73∼0.91) in early prediction of GDM. Our study demonstrated that dysregulated exosomal miRNAs in plasma from GDM pregnant women might influence the insulin and AMPK signaling pathways and could contribute to the early prediction of GDM.

中文翻译：

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与代谢相关的血浆外泌体 microRNA 作为妊娠糖尿病的早期预测因子

迄今为止，妊娠合并妊娠糖尿病 (GDM) 的女性血浆外泌体的 microRNA (miRNA) 表达谱尚未完全阐明。在这项研究中，通过高通量小 RNA 测序在 12 名 GDM 和 12 名正常葡萄糖耐量 (NGT) 孕妇中鉴定了血浆外泌体中差异表达的 miRNA，并在 102 名 GDM 和 101 名 NGT 孕妇中进行了验证。共发现 22 个外泌体 miRNA，其中 5 个通过 qRT-PCR 验证。在妊娠并发 GDM 的女性中，外泌体 miR-423-5p 被上调，而 miR-122-5p、miR-148a-3p、miR-192-5p 和 miR-99a-5p 被下调。IGF1R和GYS1作为miR-423-5p的靶基因，G6PC3和FDFT1作为miR-122-5p的靶基因，与胰岛素和 AMPK 信号通路相关，可能参与 GDM 代谢调控。五种外泌体 miRNA 在 GDM 早期预测中的 AUC 为 0.82（95%CI，0.73∼0.91）。我们的研究表明，GDM 孕妇血浆中失调的外泌体 miRNA 可能会影响胰岛素和 AMPK 信号通路，并可能有助于 GDM 的早期预测。