Scholarlink

Background <p>Sperm DNA fragmentation (SDF) is a clinically relevant marker of male reproductive potential and is frequently elevated in men with oligozoospermia. Impairment of DNA damage response and repair pathways has been implicated in increased SDF. The <i>NBN</i> (nibrin) gene, a core component of the <i>MRE11–RAD50–NBN</i> (MRN) complex, plays a critical role in the detection and repair of DNA double-strand breaks. However, the contribution of pathogenic <i>NBN</i> variants to sperm DNA integrity in oligozoospermic men remains unclear. This study aimed to evaluate whether increased SDF in oligozoospermia is associated with pathogenic variants in the <i>NBN</i> gene.</p> Methods <p>In this case–control study, 50 infertile men with oligozoospermia and 50 age-matched fertile normozoospermic controls were enrolled. SDF and chromatin condensation abnormalities were assessed using the TUNEL assay and aniline blue staining, respectively. Targeted Next-generation sequencing (NGS) was performed on peripheral blood–derived genomic DNA to analyse all coding regions and exon–intron boundaries of the <i>NBN</i> gene. Identified variants were classified according to American College of Medical Genetics and Genomics guidelines.</p> Results <p>Men with oligozoospermia exhibited significantly higher levels of SDF and chromatin condensation defects compared with fertile controls (<i>p</i> &lt; 0.001). No pathogenic or likely pathogenic variants in the <i>NBN</i> gene were identified in either group. Common benign variants were observed but did not correlate with semen parameters or DNA fragmentation levels.</p> Conclusions <p>These findings suggest that no significant association was detected between increased SDF and pathogenic <i>NBN</i> gene variants within this specific cohort. The results argue against a major independent role of <i>NBN</i> in isolated oligozoospermia-associated sperm DNA damage and suggest that alternative DNA repair pathways, epigenetic mechanisms, or non-genetic factors may contribute to impaired sperm DNA integrity. Assessment of SDF may therefore provide clinically relevant information beyond conventional semen analysis in the evaluation of male infertility.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Assessment of the association between sperm DNA fragmentation and pathogenic NBN gene variants in oligozoospermic men: a turkish case–control study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月15日

查看全文
  • Gülbahar Güzel Erdal,
  • Mahmut Balkan,
  • Selahattin Tekeş,
  • Diclehan Oral,
  • Remziye Güzel,
  • Ğarip Demir,
  • Onur Dede

摘要

Background

Sperm DNA fragmentation (SDF) is a clinically relevant marker of male reproductive potential and is frequently elevated in men with oligozoospermia. Impairment of DNA damage response and repair pathways has been implicated in increased SDF. The NBN (nibrin) gene, a core component of the MRE11–RAD50–NBN (MRN) complex, plays a critical role in the detection and repair of DNA double-strand breaks. However, the contribution of pathogenic NBN variants to sperm DNA integrity in oligozoospermic men remains unclear. This study aimed to evaluate whether increased SDF in oligozoospermia is associated with pathogenic variants in the NBN gene.

Methods

In this case–control study, 50 infertile men with oligozoospermia and 50 age-matched fertile normozoospermic controls were enrolled. SDF and chromatin condensation abnormalities were assessed using the TUNEL assay and aniline blue staining, respectively. Targeted Next-generation sequencing (NGS) was performed on peripheral blood–derived genomic DNA to analyse all coding regions and exon–intron boundaries of the NBN gene. Identified variants were classified according to American College of Medical Genetics and Genomics guidelines.

Results

Men with oligozoospermia exhibited significantly higher levels of SDF and chromatin condensation defects compared with fertile controls (p < 0.001). No pathogenic or likely pathogenic variants in the NBN gene were identified in either group. Common benign variants were observed but did not correlate with semen parameters or DNA fragmentation levels.

Conclusions

These findings suggest that no significant association was detected between increased SDF and pathogenic NBN gene variants within this specific cohort. The results argue against a major independent role of NBN in isolated oligozoospermia-associated sperm DNA damage and suggest that alternative DNA repair pathways, epigenetic mechanisms, or non-genetic factors may contribute to impaired sperm DNA integrity. Assessment of SDF may therefore provide clinically relevant information beyond conventional semen analysis in the evaluation of male infertility.