Upregulation of the Antioxidant Response-Related microRNAs miR-146a-5p and miR-21-5p in Gestational Diabetes: An Analysis of Matched Samples of Extracellular Vesicles and PBMCs

TL;DR

This study found that specific microRNAs are upregulated in gestational diabetes and may serve as indicators of oxidative stress and adverse pregnancy outcomes.

Contribution

The novel contribution is identifying miR-146a-5p and miR-21-5p as potential biomarkers for gestational diabetes and its complications.

Findings

MiR-146a-5p and miR-21-5p are significantly upregulated in GDM patients' PBMCs and EVs.

EVs-miR-21-5p correlates with glycemic status in GDM patients.

Higher PBMCs-miR-21-5p levels are linked to adverse pregnancy outcomes in GDM.

Abstract

MicroRNA-based regulatory mechanisms show disturbances related to oxidative stress (OS) interconnected with inflammation (IFM), as well as impairments associated with gestational diabetes (GDM). The aim of this study was to assess the diagnostic and prognostic significance of the OS/IFM-related microRNA in GDM by using peripheral blood mononuclear cells (PBMCs) and serum-derived extracellular vesicles (EVs) as biological samples. We selected the known OS/IFM-associated microRNAs miR-146a-5p, miR-155-5p, and miR-21-5p as candidates for our GDM biomarker analysis. Quantitative RT-PCR was employed for relative quantification of the selected microRNAs from paired samples of PBMCs and EVs derived from patients with GDM and healthy controls (n = 50 per group). The expression levels were analyzed for correlations with lipid and glycemic status indicators; metal ion-related parameters; serum thiol content; protein carbonyl and thiobarbituric acid-reactive substances’ (TBARS) levels; glutathione reductase (GR), Superoxide dismutase (SOD), and catalase (CAT) activity; and NRF2 expression. MiR-146a-5p and miR-21-5p were significantly upregulated in both PBMCs and EVs obtained from GDM patients. EVs-miR-21-5p showed a positive correlation with glycemic status in GDM patients, while miR-155-5p from PBMCs demonstrated correlation with iron-related parameters. The expression of selected microRNAs was found to correlate with NRF2 expression and SOD activity. The level of miR-146a-5p negatively correlated with neonatal anthropometric characteristics, while a higher level of PBMCs-miR-21-5p expression was determined in GDM patients with adverse pregnancy outcomes (p = 0.012). Our data demonstrate a disturbance of OS/IFM-microRNAs in GDM and illustrate their potential to serve as indicators of the associated OS-related changes, neonatal characteristics, and adverse pregnancy outcomes.

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