{
  "abstract": "Background: 6PPD-quinone (6PPD-Q), a transformation product of the tire antioxidant 6PPD, has emerged as an environmental contaminant with potential reproductive toxicity. However, its role in erectile dysfunction (ED) and the underlying mechanisms remain unclear.\n\nMethods: This study integrated network toxicology, transcriptomics, single-cell RNA sequencing, machine learning, Mendelian randomization, molecular docking, molecular dynamics simulation, and animal experiments to investigate the potential mechanisms linking 6PPD-Q exposure to ED.\n\nResults: A total of 134 genes were identified at the intersection of the 6PPD-Q- and ED-related gene sets. Integration of bulk and single-cell transcriptomic data, followed by LASSO and SVM-RFE analyses, prioritized ACO1, HIF1A, PDK4, and PTPN11. Among these genes, only HIF1A showed a significant association with ED risk in the Mendelian randomization analysis. Molecular docking and a 100-ns molecular dynamics simulation supported the structural plausibility of an interaction between 6PPD-Q and HIF-1α. In rats, 6PPD-Q exposure reduced the ICPmax/MAP ratio and cavernosal NO levels without affecting testosterone. These changes were accompanied by increased HIF-1α and decreased p-eNOS, eNOS, and p-eNOS/eNOS levels in the corpus cavernosum. PX-478 partially restored eNOS/NO signaling and erectile function.\n\nConclusion: These findings suggest that 6PPD-Q may contribute to ED by activating HIF1A-related stress responses and impairing eNOS/NO-mediated endothelial relaxation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital",
    "Department of Andrology, Nanjing Drum Tower Hospital, Affiliated hospital of Nanjing University Medical School",
    "Department of Urology, Affiliated Hospital of Southwest Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chunyang Meng"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuqi Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinyao Zhu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yifan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuelin Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongyou Xia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewrtahhdv51fr.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1912092",
  "fulltext_url": null,
  "id": "ewrtahhdv51fr",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1912092/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Sexual function and dysfunction studies"
    ]
  ],
  "openalex": "W7222419740",
  "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1912092/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ewrtahhdv51fr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1912092",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1912092/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Sexual function and dysfunction studies",
      "subfield": "psychiatry"
    }
  ],
  "title": "6PPD-quinone exposure impairs erectile function through dysregulation of the HIF-1α/eNOS/NO axis: multi-omics and in vivo evidence",
  "title_text": "6PPD-quinone exposure impairs erectile function through dysregulation of the HIF-1α/eNOS/NO axis: multi-omics and in vivo evidence",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:20Z",
  "url": "https://research.draconitic.com/paper/ewrtahhdv51fr",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}