Scholarlink

Background <p>Asthenozoospermia (AZS), a common cause of male infertility, is characterized by significantly reduced sperm motility, though its precise etiology remains unclear. Recent research highlights seminal plasma proteins’ critical role in regulating sperm function. Colony-stimulating factor 1 (CSF-1), an essential cytokine for immune regulation and cell proliferation, has been implicated in sperm functional regulation, spermatogenesis, and maturation.</p> Methods <p>Seminal plasma samples from healthy men and AZS patients were collected using density-gradient centrifugation. Proteomics-based data-independent acquisition (DIA) identified four differentially expressed proteins: CD40, CSF-1, MCP-1, and IL-20. To provide an exploratory, proof-of-concept verification before large-scale validation. Subsequent validation in an independent small cohort confirmed a robust association between elevated seminal plasma CSF-1 levels and AZS. An in vitro sperm culture system assessed CSF-1’s function of sperm from AZS patients were treated with the CSF-1 inhibitor Pexidartinib, while recombinant CSF-1 was supplemented in sperm from healthy donors.</p> Results <p>Pexidartinib treatment significantly increased sperm motility in AZS patients, whereas recombinant CSF-1 supplementation significantly reduced motility in healthy donor sperm. CSF-1 inhibition elevated intracellular ATP levels, suggesting disruption of mitochondrial energy metabolism as the mechanism for impaired motility. Proteomic profiling and functional assays demonstrated that seminal plasma CSF-1 induces mitochondrial dysfunction, thereby decreasing sperm motility.</p> Conclusion <p>Seminal-plasma CSF-1 is a potential pathogenic factor in AZS. Its overexpression suppresses sperm motility by impairing mitochondrial energy metabolism. CSF-1 represents both a diagnostic biomarker and a promising therapeutic target (e.g., via Pexidartinib) for the clinical management of AZS. These findings provide a foundation for novel diagnostic and therapeutic strategies.</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

Colony-stimulating factor-1 as a potential therapeutic target in asthenozoospermia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月22日

查看全文
  • Yongyong Wang,
  • Qi Zhou,
  • Cong Huang,
  • Xiaodong Li,
  • Haining Liu,
  • Zhongyi Sun,
  • Baoquan Han

摘要

Background

Asthenozoospermia (AZS), a common cause of male infertility, is characterized by significantly reduced sperm motility, though its precise etiology remains unclear. Recent research highlights seminal plasma proteins’ critical role in regulating sperm function. Colony-stimulating factor 1 (CSF-1), an essential cytokine for immune regulation and cell proliferation, has been implicated in sperm functional regulation, spermatogenesis, and maturation.

Methods

Seminal plasma samples from healthy men and AZS patients were collected using density-gradient centrifugation. Proteomics-based data-independent acquisition (DIA) identified four differentially expressed proteins: CD40, CSF-1, MCP-1, and IL-20. To provide an exploratory, proof-of-concept verification before large-scale validation. Subsequent validation in an independent small cohort confirmed a robust association between elevated seminal plasma CSF-1 levels and AZS. An in vitro sperm culture system assessed CSF-1’s function of sperm from AZS patients were treated with the CSF-1 inhibitor Pexidartinib, while recombinant CSF-1 was supplemented in sperm from healthy donors.

Results

Pexidartinib treatment significantly increased sperm motility in AZS patients, whereas recombinant CSF-1 supplementation significantly reduced motility in healthy donor sperm. CSF-1 inhibition elevated intracellular ATP levels, suggesting disruption of mitochondrial energy metabolism as the mechanism for impaired motility. Proteomic profiling and functional assays demonstrated that seminal plasma CSF-1 induces mitochondrial dysfunction, thereby decreasing sperm motility.

Conclusion

Seminal-plasma CSF-1 is a potential pathogenic factor in AZS. Its overexpression suppresses sperm motility by impairing mitochondrial energy metabolism. CSF-1 represents both a diagnostic biomarker and a promising therapeutic target (e.g., via Pexidartinib) for the clinical management of AZS. These findings provide a foundation for novel diagnostic and therapeutic strategies.