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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 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). 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.\n                  <\/jats:p>","DOI":"10.1186\/s12958-025-01458-0","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T12:50:07Z","timestamp":1759236607000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK\u2013PDC axis"],"prefix":"10.1186","volume":"23","author":[{"given":"Wang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Qikai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Zilin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao","family":"Junyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Xiaocui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Shuhui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Yangyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Mengjie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Siyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao","family":"Jigang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"1458_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","volume":"62","author":"M Vander Borght","year":"2018","unstructured":"Vander Borght M, Wyns C. 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