Dysregulation of microRNAs and their associations with clinical characteristics in recurrent spontaneous abortion patients

Abstract

This study aimed to identify microRNA (miRNA) expression profiles associated with recurrent spontaneous abortion (RSA) and to explore whether their dysregulation is linked to relevant clinical characteristics. A total of 51 villous specimens were collected from spontaneous abortion (SA) patients, including 31 RSA cases. Three RSA and three control specimens were randomly chosen for miRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to annotate target gene functions and related signaling pathways. Low-depth whole-genome sequencing was performed on all specimens to eliminate confounding effects induced by chromosomal karyotypic abnormalities. RT-qPCR was used to validate the expression of candidate miRNAs. Thirty-six significantly differentially expressed microRNAs were identified, consisting of 16 upregulated and 20 downregulated miRNAs. The proportion of abnormal chromosomal karyotypes was significantly higher in women with a single spontaneous abortion than in those with two or more spontaneous abortions ( p  < 0.001). The relative expression levels of miR-182-5p, miR-2110, and miR-320a-3p was not significantly different between samples with normal and abnormal karyotype. The expression levels of miR-182-5p and miR-2110 in the villi of the RSA group were significantly lower than those in the control group (0.736 ± 0.139 vs. 1.830 ± 0.480, p  < 0.01; 1.874 ± 0.476 vs. 2.493 ± 0.582, p  < 0.05, respectively). No significant difference was observed for miR-320a-3p expression between the RSA and control groups. Similarly, when the primary RSA subgroup was compared with the control group, comparable results were obtained for miR-182-5p, miR-2110, and miR-320a-3p. Notably, the expression level of miR-320a-3p was significantly upregulated in the high BMI group compared with the normal BMI group ( p  < 0.05). Two major findings emerged from this study. First, miR-182-5p and miR-2110 are associated with RSA, particularly primary RSA. Second, miR-320a-3p appears to indirectly affect reproductive outcomes by participating in obesity-related metabolic pathways, rather than acting as a direct disease-specific marker for RSA. Collectively, these findings suggest that These findings suggest that miR-182-5p and miR-2110 may serve as potential biomarkers for RSA, while miR-320a-3p may reflect obesity-related metabolic status.