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<p>Male infertility, a significant global public health challenge, arises from multifactorial interactions involving genetic, metabolic, and psychological factors. While psychological stress (depression/anxiety/stress, DAS) is increasingly linked to impaired sperm quality, its molecular mechanisms remain unclear. This cross-sectional study investigates mitochondrial metabolic reprogramming via the pyruvate dehydrogenase kinase (PDK)-pyruvate dehydrogenase complex (PDC) axis under psychological stress, exploring multidimensional impacts on semen quality.Approved by three tertiary hospitals in Central China, 557 participants were categorized into DAS and non-DAS groups based on DASS-21 scores, with clinical histories and semen samples collected. Targeted metabolomics (ATP/pyruvate/lactate), lipidomics (free fatty acids), and RT-qPCR (PDK1-4, PDH mRNA) were performed. Results revealed significantly reduced sperm motility in the DAS group (<i>p</i> &lt; 0.01). Mechanistically, DAS upregulated PDK2/PDK4 expression and suppressed PDH expression, driving metabolic reprogramming and mitochondrial dysfunction. This study provides the first evidence that psychological stress impairs sperm motility via PDK-PDC axis dysregulation, offering novel mechanistic insights and potential therapeutic targets for male infertility.</p>

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Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK–PDC axis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月30日

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  • Wang Wang,
  • Wang Qikai,
  • Wang Zilin,
  • Shao Junyan,
  • Jiang Xiaocui,
  • Liu Qi,
  • Chen Shuhui,
  • Zhu Yangyang,
  • Gao Mengjie,
  • Chen Siyi,
  • Cao Jigang,
  • Xiao Min

摘要

Male infertility, a significant global public health challenge, arises from multifactorial interactions involving genetic, metabolic, and psychological factors. While psychological stress (depression/anxiety/stress, DAS) is increasingly linked to impaired sperm quality, its molecular mechanisms remain unclear. This cross-sectional study investigates mitochondrial metabolic reprogramming via the pyruvate dehydrogenase kinase (PDK)-pyruvate dehydrogenase complex (PDC) axis under psychological stress, exploring multidimensional impacts on semen quality.Approved by three tertiary hospitals in Central China, 557 participants were categorized into DAS and non-DAS groups based on DASS-21 scores, with clinical histories and semen samples collected. Targeted metabolomics (ATP/pyruvate/lactate), lipidomics (free fatty acids), and RT-qPCR (PDK1-4, PDH mRNA) were performed. Results revealed significantly reduced sperm motility in the DAS group (p < 0.01). Mechanistically, DAS upregulated PDK2/PDK4 expression and suppressed PDH expression, driving metabolic reprogramming and mitochondrial dysfunction. This study provides the first evidence that psychological stress impairs sperm motility via PDK-PDC axis dysregulation, offering novel mechanistic insights and potential therapeutic targets for male infertility.