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Background <p>The testis exhibits the highest tissue-specific gene expression of all organs, including both coding and non-coding genes. Our previous study reported that <i>Teshl</i>, a testis-specific long noncoding RNA, associates with heat shock factor 2 (HSF2), a transcription factor, to regulate Y chromosome gene expression and sperm fertility.</p> Results <p>We conducted an in-depth analysis of the function and molecular mechanisms of <i>Teshl</i> using <i>Teshl</i>-knockout (KO) mice. Remarkably, the absence of <i>Teshl</i> caused abnormal acrosome biogenesis during spermiogenesis, resulting in malformed and disorganized acrosomes and abnormal sperm head morphology. <i>Teshl</i>-KO sperm also exhibited altered acrosome reaction and reduced motility. A thorough examination of all available relevant datasets identified three <i>Teshl</i>-related proteins associated with acrosome structure and function: actin related protein T1 (ACTRT1), acrosin binding protein (ACRBP) and dickkopf-like acrosomal protein 1 (DKKL1). Our findings suggest that these proteins are directly or indirectly regulated by <i>Teshl</i>-HSF2 through transcriptional or protein-interaction mechanisms.</p> Conclusions <p>The present findings significantly expand our understanding of the important roles of <i>Teshl</i>, a pioneering testis-specific lncRNA, by elucidating its acrosomal function and mechanism in male reproduction.</p>

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Testis-specific lncRNA Teshl regulates acrosome biogenesis to maintain sperm structure and function

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月30日

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  • Seung Pyo Hong,
  • Seong Hyeon Hong,
  • Gwidong Han,
  • Seung Jae Lee,
  • Youngsoo Oh,
  • Chunghee Cho

摘要

Background

The testis exhibits the highest tissue-specific gene expression of all organs, including both coding and non-coding genes. Our previous study reported that Teshl, a testis-specific long noncoding RNA, associates with heat shock factor 2 (HSF2), a transcription factor, to regulate Y chromosome gene expression and sperm fertility.

Results

We conducted an in-depth analysis of the function and molecular mechanisms of Teshl using Teshl-knockout (KO) mice. Remarkably, the absence of Teshl caused abnormal acrosome biogenesis during spermiogenesis, resulting in malformed and disorganized acrosomes and abnormal sperm head morphology. Teshl-KO sperm also exhibited altered acrosome reaction and reduced motility. A thorough examination of all available relevant datasets identified three Teshl-related proteins associated with acrosome structure and function: actin related protein T1 (ACTRT1), acrosin binding protein (ACRBP) and dickkopf-like acrosomal protein 1 (DKKL1). Our findings suggest that these proteins are directly or indirectly regulated by Teshl-HSF2 through transcriptional or protein-interaction mechanisms.

Conclusions

The present findings significantly expand our understanding of the important roles of Teshl, a pioneering testis-specific lncRNA, by elucidating its acrosomal function and mechanism in male reproduction.