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Abstract：
The high incidence of idiopathic recurrent pregnancy loss (iRPL) may stem from the limited research on male contributory factors. Many studies suggest that sperm DNA fragmentation and oxidative stress contribute to iRPL, but their roles are still debated. MicroRNAs (miRNAs) are short non-coding RNAs that regulate various biological processes by modulating gene expression. While differential expression of specific miRNAs has been observed in women suffering from recurrent miscarriages, paternal miRNAs remain unexplored. We hypothesize that analyzing sperm miRNAs can provide crucial insights into the pathophysiology of iRPL. Therefore, this study aims to identify dysregulated miRNAs in the spermatozoa of male partners of iRPL patients. Total mRNA was extracted from sperm samples of iRPL and control groups, followed by miRNA library preparation and high-output miRNA sequencing. Subsequently, raw sequence reads were processed for differential expression analysis, target prediction, and bioinformatics analysis. Twelve differentially expressed miRNAs were identified in the iRPL group, with eight miRNAs upregulated (hsa-miR-4454, hsa-miR-142-3p, hsa-miR-145-5p, hsa-miR-1290, hsa-miR-1246, hsa-miR-7977, hsa-miR-449c-5p, and hsa-miR-92b-3p) and four downregulated (hsa-miR-29c-3p, hsa-miR-30b-5p, hsa-miR-519a-2-5p, and hsa-miR-520b-5p). Functional enrichment analysis revealed that gene targets of the upregulated miRNAs are involved in various biological processes closely associated with sperm quality and embryonic development.
摘要：
特发性复发性妊娠丢失（iRPL）的高发生率可能源于对男性促成因素的有限研究。许多研究表明，精子DNA断裂和氧化应激有助于iRPL，但他们的角色仍在争论中。MicroRNAs(miRNA)是短的非编码RNA,其通过调节基因表达来调节各种生物过程。虽然在复发性流产的女性中观察到特定miRNA的差异表达，父系miRNA仍未被探索。我们假设分析精子miRNAs可以为iRPL的病理生理学提供重要的见解。因此,这项研究旨在鉴定iRPL患者男性伴侣精子中失调的miRNAs。从iRPL和对照组的精子样本中提取总mRNA，其次是miRNA文库制备和高输出miRNA测序。随后，原始序列读取进行差异表达分析，目标预测，和生物信息学分析。在iRPL组中鉴定出12个差异表达的miRNA,与八个miRNA上调（hsa-miR-4454，hsa-miR-142-3p，hsa-miR-145-5p,hsa-miR-1290,hsa-miR-1246,hsa-miR-7977,hsa-miR-449c-5p,和hsa-miR-92b-3p）和四个下调（hsa-miR-29c-3p，hsa-miR-30b-5p,hsa-miR-519a-2-5p,和hsa-miR-520b-5p）。功能富集分析表明，上调的miRNAs的基因靶标参与与精子质量和胚胎发育密切相关的各种生物过程。
