Scholarlink

Purpose <p>Hypospadias, a prevalent congenital anomaly characterized by abnormal urethral opening formation, poses significant psychological and physical challenges to patients. This study aimed to elucidate the function of extrachromosomal circular DNA (eccDNA) found in foreskin tissues of hypospadias patients as well as its association with immunoinflammatory responses and microbial dynamics.</p> Methods <p>We used Circle-seq to quantify eccDNA abundance and RNA sequencing for gene expression profiling. Foreskin samples were carefully collected from 54 patients with hypospadias and compared against samples from 59 control individuals with phimosis. The hypospadias cohort was significantly younger (mean 3.2&#xa0;years) than controls (mean 7.5&#xa0;years), which might be a major limitation that confounded immune and microbiome findings and limited causal interpretation. Tissue samples were collected after standard surgical disinfection, which may influence microbial detection.</p> Results <p>Our analysis revealed a striking increase in eccDNA abundance, identifying 2,387,050 eccDNA elements in the hypospadias cohort, contrasted with only 608,545 in the control group. Furthermore, gene expression profiling demonstrated the up-regulation of 541 genes and the down-regulation of 257 genes, with significant enrichment in pathways related to inflammatory responses and lymphocyte differentiation, indicating dysregulated immune responses in hypospadias. Complementary findings of elevated white blood cell counts and inflammatory cytokines underscored the heightened immunoinflammatory response associated with this condition. The activated immunoinflammatory response showed positive associations with eccDNA abundance and sizes. Notably, microbial profiling uncovered that Escherichia coli constituted 43.11% of the foreskin microbiome in hypospadias patients, considerably exceeding levels found in phimosis. Escherichia coli abundance was associated with increased immunoinflammatory response and higher eccDNA levels.</p> Conclusion <p>This study underscores a complex association between immunoinflammatory responses and microbial communities in the pathophysiology of eccDNA dynamics in hypospadias, revealing important implications for future research and potential therapeutic strategies.</p> Graphical abstract <p></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

Integrated analysis of extrachromosomal circular DNA and transcriptome reveals associations between microbial profiles and Immunoinflammatory markers in hypospadias

  • 期刊论文

  • 发表日期：

    2026年2月16日

查看全文
  • Zhilin Yang,
  • Jiaying Yu,
  • Xiaoning Hong,
  • Jianchun Yin,
  • Tiejun Zhang,
  • Changze Song,
  • Chunxiao He,
  • Shuang Mao,
  • Huisheng Yuan,
  • Peng Han,
  • Jiang Li,
  • Xi Xiang,
  • Shoulin Li,
  • Zilong Wang

摘要

Purpose

Hypospadias, a prevalent congenital anomaly characterized by abnormal urethral opening formation, poses significant psychological and physical challenges to patients. This study aimed to elucidate the function of extrachromosomal circular DNA (eccDNA) found in foreskin tissues of hypospadias patients as well as its association with immunoinflammatory responses and microbial dynamics.

Methods

We used Circle-seq to quantify eccDNA abundance and RNA sequencing for gene expression profiling. Foreskin samples were carefully collected from 54 patients with hypospadias and compared against samples from 59 control individuals with phimosis. The hypospadias cohort was significantly younger (mean 3.2 years) than controls (mean 7.5 years), which might be a major limitation that confounded immune and microbiome findings and limited causal interpretation. Tissue samples were collected after standard surgical disinfection, which may influence microbial detection.

Results

Our analysis revealed a striking increase in eccDNA abundance, identifying 2,387,050 eccDNA elements in the hypospadias cohort, contrasted with only 608,545 in the control group. Furthermore, gene expression profiling demonstrated the up-regulation of 541 genes and the down-regulation of 257 genes, with significant enrichment in pathways related to inflammatory responses and lymphocyte differentiation, indicating dysregulated immune responses in hypospadias. Complementary findings of elevated white blood cell counts and inflammatory cytokines underscored the heightened immunoinflammatory response associated with this condition. The activated immunoinflammatory response showed positive associations with eccDNA abundance and sizes. Notably, microbial profiling uncovered that Escherichia coli constituted 43.11% of the foreskin microbiome in hypospadias patients, considerably exceeding levels found in phimosis. Escherichia coli abundance was associated with increased immunoinflammatory response and higher eccDNA levels.

Conclusion

This study underscores a complex association between immunoinflammatory responses and microbial communities in the pathophysiology of eccDNA dynamics in hypospadias, revealing important implications for future research and potential therapeutic strategies.

Graphical abstract