Hashemi Karoii Danial, Abroudi Ali Shakeri, Darvar Maryam, Djamali Melika, Azizi Hossein, Skutella Thomas
Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran; Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran.
Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Genomics. 2025 May;117(3):111046. doi: 10.1016/j.ygeno.2025.111046. Epub 2025 Apr 23.
Non-obstructive azoospermia (NOA) is a severe form of male infertility, yet its underlying molecular mechanisms remain poorly understood. This study aimed to identify key regulatory non-coding RNAs (ncRNAs) and hub genes associated with NOA through an integrative bioinformatics approach. Using microarray analysis, we examined 4956 ncRNAs and identified 29 differentially expressed ncRNAs (14 upregulated, 15 downregulated) in NOA compared to healthy individuals. Co-expression analysis revealed significant interactions between lncRNAs, miRNAs, and mRNAs, predicting 31 target mRNAs within the regulatory network. Further, single-cell transcriptomic analysis identified four pivotal hub genes in NOA Sertoli cells: CLTC, XIAP, and DHFR (upregulated) and STMN1 (downregulated). Functional enrichment analysis highlighted critical pathways, including mitotic spindle organization and phosphatase activity, suggesting their involvement in NOA pathophysiology. Our findings provide novel insights into the molecular mechanisms underlying NOA and propose potential biomarkers for improved diagnosis and therapeutic strategies.
非梗阻性无精子症（NOA）是男性不育的一种严重形式，但其潜在的分子机制仍知之甚少。本研究旨在通过综合生物信息学方法鉴定与NOA相关的关键调控非编码RNA（ncRNA）和枢纽基因。通过微阵列分析，我们检测了4956个ncRNA，并鉴定出与健康个体相比，NOA中有29个差异表达的ncRNA（14个上调，15个下调）。共表达分析揭示了lncRNA、miRNA和mRNA之间的显著相互作用，预测了调控网络中的31个靶mRNA。此外，单细胞转录组分析确定了NOA支持细胞中的四个关键枢纽基因：CLTC、XIAP和DHFR（上调）以及STMN1（下调）。功能富集分析突出了关键途径，包括有丝分裂纺锤体组织和磷酸酶活性，表明它们参与了NOA的病理生理过程。我们的数据为NOA潜在的分子机制提供了新见解，并提出了用于改善诊断和治疗策略的潜在生物标志物。
