{
  "abstract": "Varicocele (VCL) is a major cause of male infertility and is closely associated with oxidative stress (OS)-induced testicular injury. Increasing evidence suggests that endoplasmic reticulum stress (ERS) interacts with OS and mitochondrial dysfunction in the pathogenesis of spermatogenic impairment, but the molecular regulators linking these processes remain incompletely understood. In this study, we investigated the role of Nupr1 in VCL-related testicular stress responses. Re-analysis of transcriptomic data from VCL rat testes identified Nupr1 as a candidate gene associated with OS, ERS, and apoptosis. Nupr1 expression was significantly increased in VCL testes and was similarly upregulated in GC-2 and TM4 cells under H2O2-induced OS or tunicamycin-induced ERS. Stable knockdown of Nupr1 in GC-2 cells reduced viability under oxidative challenge, increased intracellular ROS accumulation, decreased mitochondrial membrane potential, and enhanced apoptosis, accompanied by increased cleaved caspase-3 expression and an elevated Bax/Bcl-2 ratio. Notably, Nupr1 deficiency attenuated the adaptive ERS response, as shown by reduced expression of GRP78, IRE1/p-IRE1, PERK/p-PERK, and ATF6. Pharmacological induction of ERS with tunicamycin further worsened cell injury in Nupr1-deficient cells, whereas 4-PBA failed to restore cell viability or GRP78 expression. Collectively, these findings indicate that Nupr1 is involved in the cellular stress response relevant to VCL and may help maintain adaptive UPR signaling and mitochondrial homeostasis in spermatogenic cells under oxidative stress.",
  "abstract_shown": true,
  "affiliations": [
    "School of Life Sciences, Bengbu Medical University, Bengbu, China",
    "Anhui Engineering Research Center for Neural Regeneration Technology and Medical New Materials, Bengbu Medical University, Bengbu, China",
    "School of Clinical Medicine, Bengbu Medical University, Bengbu, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xue Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lemin Tang"
    },
    {
      "affs": [
        2
      ],
      "name": "Zuzhi Ma"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinping Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenwei Nian"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianxiang Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yaping Liao",
      "orcid": "0000-0003-2632-5463"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bdv30nb1jqe0z.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359950",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734504/",
  "id": "bdv30nb1jqe0z",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359950",
  "language": "en",
  "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": [
    [
      "heading",
      "Anatomy"
    ],
    [
      "heading",
      "Apoptosis"
    ],
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Bioenergetics"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Cell Death"
    ],
    [
      "heading",
      "Cell Processes"
    ],
    [
      "heading",
      "Cellular Stress Responses"
    ],
    [
      "heading",
      "Cellular Structures and Organelles"
    ],
    [
      "heading",
      "Endoplasmic Reticulum"
    ],
    [
      "heading",
      "Energy-Producing Organelles"
    ],
    [
      "heading",
      "Fluorescence Imaging"
    ],
    [
      "heading",
      "Gene Expression"
    ],
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Genital Anatomy"
    ],
    [
      "heading",
      "Homeostasis"
    ],
    [
      "heading",
      "Imaging Techniques"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Mitochondria"
    ],
    [
      "heading",
      "Physiological Processes"
    ],
    [
      "heading",
      "Physiology"
    ],
    [
      "heading",
      "Reproductive System"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Research and Analysis Methods"
    ],
    [
      "heading",
      "Secretory Pathway"
    ],
    [
      "heading",
      "Testes"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Reproductive system/Genital anatomy/Testes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Bioenergetics/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Apoptosis"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cellular stress responses"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Secretory pathway/Endoplasmic reticulum"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Endoplasmic reticulum"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Homeostasis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Reproductive system/Genital anatomy/Testes"
    ],
    [
      "plos",
      "/Research and analysis methods/Imaging techniques/Fluorescence imaging"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": "PMC13734504",
  "pmid": "42981290",
  "published": "2026-11-04",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/bdv30nb1jqe0z.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:11Z",
      "native_id": "10.1371/journal.pone.0359950",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359950"
    },
    {
      "first_seen": "2026-11-08T12:24:00Z",
      "native_id": "PMC13734504",
      "source": "pmc",
      "url": "https://doi.org/10.1371/journal.pone.0359950"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Gene Expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "heading:Genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "In vivo Nupr1 regulates oxidative stress–endoplasmic reticulum stress crosstalk and mitochondria-dependent apoptosis in varicocele-related testicular injury",
  "title_text": "In vivo Nupr1 regulates oxidative stress–endoplasmic reticulum stress crosstalk and mitochondria-dependent apoptosis in varicocele-related testicular injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:24:00Z",
  "url": "https://research.draconitic.com/paper/bdv30nb1jqe0z",
  "venue": "PLOS One",
  "versions": []
}