Reduced Sperm miR-34c-5p Expression as a Potential Risk Factor for Unexplained Recurrent Miscarriage

We aimed to investigate the correlation between differential miRNA expression in sperm and unexplained recurrent miscarriage. Semen samples were collected from 22 partners of patients with unexplained recurrent miscarriage at the Affiliated Hospital of Inner Mongolia Medical University between July 2021 and February 2023, and compared with those from 19 healthy male controls who were planning to conceive during the same period. miRNA sequencing was performed to analyse the differential expression of miRNAs in semen samples. Three paternal miRNAs were selected for reverse transcription polymerase chain reaction (RT–PCR) validation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of miR-34c-5p were conducted. We identified 90 differentially expressed miRNAs in sperm from the case group, 4 of which were paternal miRNAs in the embryo. RT–PCR revealed significantly low miR-34c-5p expression ( p  < 0.001), with its target genes primarily associated with cellular membrane components and nervous system processes. miR-34c-5p was mostly enriched in the Notch and Rap1 signaling pathways. Binary logistic regression analysis indicated low hsa-miR-34c-5p expression as a high-risk factor for recurrent miscarriage (odds ratio = 4.344; 95% confidence interval, 1.119–16.857; p  < 0.05). These findings provide novel insights into the underlying mechanisms of unexplained recurrent miscarriage.