Thapliyal Ayushi, Tomar Anil Kumar, Naglot Sarla, Dhiman Soniya, Datta Sudip Kumar, Sharma Jai Bhagwan, Singh Neeta, Yadav Savita
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Division of Reproductive, Child Health and Nutrition, Indian Council of Medical Research (ICMR), New Delhi 110029, India.
Noncoding RNA. 2024 Jul 21;10(4):41. doi: 10.3390/ncrna10040041.
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.
特发性复发性流产（iRPL）的高发生率可能源于对男性促成因素的研究有限。许多研究表明，精子DNA片段化和氧化应激与iRPL有关，但其作用仍存在争议。微小RNA（miRNA）是短链非编码RNA，通过调节基因表达来调控各种生物学过程。虽然在反复流产的女性中观察到特定miRNA的差异表达，但父系miRNA仍未被探索。我们假设分析精子miRNA可以为iRPL的病理生理学提供关键见解。因此，本研究旨在鉴定iRPL患者男性伴侣精子中失调的miRNA。从iRPL组和对照组的精子样本中提取总mRNA，随后制备miRNA文库并进行高通量miRNA测序。随后，对原始序列读数进行差异表达分析、靶标预测和生物信息学分析。在iRPL组中鉴定出12种差异表达的miRNA，其中8种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），4种下调（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miRNA的基因靶标参与了与精子质量和胚胎发育密切相关的各种生物学过程。
