Implicating Sperm microRNA hsa-miR-7977 and its Target Genes in Idiopathic Recurrent Pregnancy Loss: Evidence from Expression Analysis.

Nearly half of recurrent pregnancy loss (RPL) cases lack an identifiable cause and are classified as idiopathic RPL (iRPL), posing considerable emotional and financial burdens on affected couples. While maternal contributions to RPL have been extensively studied, the role of paternal molecular factors remains inadequately understood. Recent evidence points to the involvement of sperm-borne molecules, such as microRNAs, in the pathogenesis of iRPL. In our previous work, we identified 12 dysregulated microRNAs in spermatozoa from male partners of women with iRPL, including hsa-miR-7977. This study focused on evaluating the expression of hsa-miR-7977 and its target genes using quantitative real-time PCR. Bioinformatic analysis predicted 1,276 targets, of which 771 were selected for functional annotation, and pathway analysis. These genes are linked to some of the key biological processes, including transcriptional regulation, intracellular signal transduction, protein complex assembly, nuclear protein localization, and phosphorylation. The interaction network revealed limited connectivity among these targets, suggesting miR-7977 may regulate functionally diverse proteins. Of the 20 identified hub genes, eight were selected based on their relevance to male reproductive physiology and fertilization-related processes. Expression analysis showed significant upregulation of hsa-miR-7977 and downregulation of BCL2 and MDM2, two critical apoptosis regulators. Reduced expression of these genes may result in the disruption of apoptotic pathways, leading to increased sperm DNA fragmentation. In conclusion, these findings suggest that overexpression of hsa-miR-7977 may impair sperm function and embryonic development, potentially through increased sperm DNA fragmentation, thereby contributing to pregnancy loss.