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Background <p>Infertility affects 50–80&#xa0;million individuals globally (WHO), with male factors, particularly abnormal semen parameters, contributing to 50% of cases. Among these, impaired sperm motility (asthenozoospermia, AZ) critically compromises fertilization potential. This study aimed to identify molecular biomarkers for AZ by investigating gene and competing endogenous RNA (ceRNA) networks associated with sperm motility.</p> Methods <p>The study population included 100 participants, including 50 AZ and 50 Normozoospermia (NZ, control), according to the semen criteria (WHO 2021). We integrated bioinformatics analyses, including differential gene expression profiling (Gene Expression Omnibus dataset), protein-protein interaction (PPI) networks, and miRNA-lncRNA-mRNA regulatory networks. Candidate biomarkers were experimentally validated via qRT-PCR and receiver operating characteristic (ROC) curve analyses in AZ patients.</p> Results <p>An integrated bioinformatics and experimental approach identified <i>AKT1</i>, <i>hsa-miR-1286</i>, and <i>LINC00242</i> as a putative network associated with sperm motility that warrants further functional validation. QRT-PCR validation demonstrated significant downregulation of <i>AKT1</i> and <i>hsa-miR-1286</i>, alongside upregulation of <i>LINC00242</i> in AZ samples. Expression levels of AKT1 and <i>hsa-miR-1286</i> showed positive correlations with sperm motility, whereas <i>LINC00242</i> exhibited a strong negative correlation. ROC curve analysis further suggests preliminary diagnostic potential of these molecules.</p> Conclusions <p>Key findings suggested that <i>AKT1</i>, <i>hsa-miR-1286</i>, and <i>linc00242</i> may represent preliminary diagnostic molecules, with the <i>hsa-miR-1286/linc00242/AKT1</i> relationship emerging as a putative expression associated network linked to sperm motility.</p>

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Identification of AKT1 and related ncRNAs hsa-miR-1286 and linc00242 as a putative molecular pathway in men with asthenozoospermia

  • 期刊论文

  • 发表日期：

    2026年2月4日

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  • Mohammadreza Saberiyan,
  • S. M. Kalantar,
  • Reza Mirfakhraie,
  • Hossein Teimori,
  • Naser Riazi,
  • Fatemeh Taheri,
  • Azim Nejatizadeh

摘要

Background

Infertility affects 50–80 million individuals globally (WHO), with male factors, particularly abnormal semen parameters, contributing to 50% of cases. Among these, impaired sperm motility (asthenozoospermia, AZ) critically compromises fertilization potential. This study aimed to identify molecular biomarkers for AZ by investigating gene and competing endogenous RNA (ceRNA) networks associated with sperm motility.

Methods

The study population included 100 participants, including 50 AZ and 50 Normozoospermia (NZ, control), according to the semen criteria (WHO 2021). We integrated bioinformatics analyses, including differential gene expression profiling (Gene Expression Omnibus dataset), protein-protein interaction (PPI) networks, and miRNA-lncRNA-mRNA regulatory networks. Candidate biomarkers were experimentally validated via qRT-PCR and receiver operating characteristic (ROC) curve analyses in AZ patients.

Results

An integrated bioinformatics and experimental approach identified AKT1, hsa-miR-1286, and LINC00242 as a putative network associated with sperm motility that warrants further functional validation. QRT-PCR validation demonstrated significant downregulation of AKT1 and hsa-miR-1286, alongside upregulation of LINC00242 in AZ samples. Expression levels of AKT1 and hsa-miR-1286 showed positive correlations with sperm motility, whereas LINC00242 exhibited a strong negative correlation. ROC curve analysis further suggests preliminary diagnostic potential of these molecules.

Conclusions

Key findings suggested that AKT1, hsa-miR-1286, and linc00242 may represent preliminary diagnostic molecules, with the hsa-miR-1286/linc00242/AKT1 relationship emerging as a putative expression associated network linked to sperm motility.