Exosome miRNA Profiles: The Reduced Expression of miRNA‐27a‐5p and Predictive miRNAs for Gestational Diabetes Mellitus

ABSTRACT Gestational diabetes mellitus (GDM) poses both short‐term and long‐term health risks to mothers and infants. This study aims to examine the mechanisms involving insulin resistance mediated by exosomal miRNAs. We enrolled 2284 pregnant women from First People's Hospital of Kunshan, Jiangsu Province in this continuous follow‐up study. Plasma exosomes from patients with GDM and healthy pregnancies during the first trimester were co‐cultured with human choriocarcinoma (JEG‐3) cell lines. Plasma exosome samples collected at 8–12 and 24–28 gestational weeks were analyzed using high‐throughput small‐RNA sequencing. The expression levels of exosomal miRNAs were validated via real‐time polymerase chain reaction. Receiver operating characteristic (ROC) analysis was employed to assess their potential as early predictors. Plasma exosomes from the GDM group exhibited lower expressions of Let‐7c‐5p and miR‐27a‐5p compared to those from normal pregnancies by sequencing and validation during early pregnancy ( p < 0.05). These changes may influence the development and growth of JEG‐3 cells. miR‐122‐5p expression was elevated in GDM cases. The expression trajectories of these three miRNAs declined from early to late pregnancy. This miRNA panel showed potential as an early predictive biomarker for GDM (area under the ROC curve, 0.844; p < 0.05). Our findings demonstrate the significant role of exosomal miRNAs in GDM's pathogenesis and reveal a novel pattern of miRNA expression decline from early to late pregnancy. These miRNAs, particularly in combination, may be used as potential predictive biomarkers for GDM.