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<p>Non-obstructive azoospermia (NOA) is a critical subtype of male infertility associated with inflammation. However, the molecular mechanisms underlying this phenomenon remain poorly understood. This study investigated the role of the inflammation-activated long non-coding RNA <i>SNHG1</i> in NOA pathogenesis. Using lipopolysaccharide (LPS)-induced orchitis mouse models and spermatogonium cell lines (GC-1 spg and TCAM-2), we observed that both <i>SNHG1</i> and the transcription factor <i>SP1</i> were significantly upregulated, correlating with spermatogonium proliferation and loss of stemness. Mechanistically, <i>SP1</i> directly binds to and transcriptionally activates the <i>SNHG1</i> promoter, whereas <i>SNHG1</i> knockdown rescued LPS-induced spermatogonium dysfunction without affecting <i>SP1</i> expression. RNA-seq revealed that <i>SNHG1</i> overexpression activated the <i>IL-17&#xa0;A</i> signaling pathway. Notably, <i>IL-17&#xa0;A</i> receptor blockade (Brodalumab) reversed the <i>SNHG1</i>-mediated proliferation arrest and stemness. Our findings demonstrated that the <i>SP1-SNHG1-IL-17&#xa0;A</i> axis drives inflammatory spermatogenic failure, suggesting <i>IL-17&#xa0;A</i> inhibition as a potential therapeutic direction.</p> Graphical Abstract <p>In lipopolysaccharide-induced orchitis mouse models and spermatogonial cell lines, <i>SP1</i> directly binds to and transcriptionally activates the <i>SNHG1</i> promoter, whereas <i>SNHG1</i> regulates spermatogonial development via the <i>IL-17&#xa0;A</i> signaling pathway.</p> <p></p>

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Inflammation-induced LncRNA SNHG1 orchestrates spermatogonium development in non-obstructive azoospermia via IL-17 A signaling pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月6日

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  • Yongtong Zhu,
  • Maocai Li,
  • Xiaomin Zhan,
  • Li Liu,
  • Cairong Chen,
  • Yao Zhou,
  • Pei He,
  • Rui Hua

摘要

Non-obstructive azoospermia (NOA) is a critical subtype of male infertility associated with inflammation. However, the molecular mechanisms underlying this phenomenon remain poorly understood. This study investigated the role of the inflammation-activated long non-coding RNA SNHG1 in NOA pathogenesis. Using lipopolysaccharide (LPS)-induced orchitis mouse models and spermatogonium cell lines (GC-1 spg and TCAM-2), we observed that both SNHG1 and the transcription factor SP1 were significantly upregulated, correlating with spermatogonium proliferation and loss of stemness. Mechanistically, SP1 directly binds to and transcriptionally activates the SNHG1 promoter, whereas SNHG1 knockdown rescued LPS-induced spermatogonium dysfunction without affecting SP1 expression. RNA-seq revealed that SNHG1 overexpression activated the IL-17 A signaling pathway. Notably, IL-17 A receptor blockade (Brodalumab) reversed the SNHG1-mediated proliferation arrest and stemness. Our findings demonstrated that the SP1-SNHG1-IL-17 A axis drives inflammatory spermatogenic failure, suggesting IL-17 A inhibition as a potential therapeutic direction.

Graphical Abstract

In lipopolysaccharide-induced orchitis mouse models and spermatogonial cell lines, SP1 directly binds to and transcriptionally activates the SNHG1 promoter, whereas SNHG1 regulates spermatogonial development via the IL-17 A signaling pathway.