{
  "abstract": "Background\n\nNonobstructive azoospermia (NOA) is characterized by impaired spermatogenesis, yet the molecular mechanisms regulating spermatogonial stem cells (SSCs) in NOA remain unclear. Forkhead box protein P1 (FOXP1), a transcription factor implicated in cell proliferation and differentiation, may play a critical role in SSC function.Methods\n\nTesticular tissues from OA and NOA patients were examined for FOXP1 expression using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Cell viability, proliferation, and apoptosis were assessed by CCK-8, EdU, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The interaction between the FOXP1 and GSK3B promoter was analyzed via bioinformatics, chromatin immunoprecipitation, and luciferase reporter assays. Western blotting evaluated Wnt/β-catenin pathway activation. The role of this pathway was further confirmed by LiCl treatment in FOXP1-silenced SSCs.Results\n\nFOXP1 was downregulated in NOA samples displaying defective spermatogenesis. FOXP1 knockdown inhibited SSC viability and proliferation while promoting apoptosis. Mechanistically, FOXP1 bound directly to the GSK3B promoter, repressing its transcription. Silencing FOXP1 increased GSK3B expression and suppressed Wnt/β-catenin signaling. Activation of Wnt/β-catenin by LiCl reversed the detrimental effects of FOXP1 knockdown on SSCs.Conclusion\n\nFOXP1 positively regulates SSC proliferation and survival by transcriptionally repressing GSK3B and maintaining Wnt/β-catenin signaling. These findings highlight that the FOXP1-GSK3B-Wnt/β-catenin signaling axis plays an essential role in maintaining SSC homeostasis and spermatogenic function and provides novel mechanistic insights into the molecular pathogenesis of NOA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Andrology and Sexual Medicine The First Affiliated Hospital of Fujian Medical University Fuzhou China fjmu.edu.cn.",
    "Reproductive Medicine Department Ganzhou Hospital-Nanfang Hospital Southern Medical University (Ganzhou People's Hospital) Ganzhou China fimmu.com.",
    "Department of Andrology Ganzhou Hospital-Nanfang Hospital Southern Medical University (Ganzhou People's Hospital) Ganzhou China fimmu.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jin-Hua Wu",
      "orcid": "0009-0001-5068-6755"
    },
    {
      "affs": [
        1
      ],
      "name": "Qing Feng"
    },
    {
      "affs": [
        2
      ],
      "name": "Feng Lin"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiang-Ping Xie"
    },
    {
      "affs": [
        2
      ],
      "name": "Pei-Yan Liu",
      "orcid": "0009-0000-9180-9080"
    },
    {
      "affs": [
        2
      ],
      "name": "Yan-Hua Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui-Liang Zhou",
      "orcid": "0000-0002-7154-3657"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/28x9kcqt41fkz.bib",
  "cited_by": 0,
  "doi": "10.1155/sci/1109631",
  "fulltext_url": "https://europepmc.org/articles/PMC13681013",
  "id": "28x9kcqt41fkz",
  "issns": [
    "1687-966X",
    "1687-9678"
  ],
  "landing_url": "https://europepmc.org/article/MED/42903529",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2743|Sperm and Testicular Function"
    ]
  ],
  "openalex": "W7223030312",
  "pdf_url": "https://europepmc.org/articles/PMC13681013?pdf=render",
  "pmcid": "PMC13681013",
  "pmid": "42903529",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/28x9kcqt41fkz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42903529",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903529"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2743|Sperm and Testicular Function",
      "subfield": "reproductive-child"
    }
  ],
  "title": "FOXP1 Promotes Spermatogonial Stem Cell Proliferation by Transcriptionally Repressing GSK3B to Activate the Wnt/β-Catenin Signaling Pathway.",
  "title_text": "FOXP1 Promotes Spermatogonial Stem Cell Proliferation by Transcriptionally Repressing GSK3B to Activate the Wnt/β-Catenin Signaling Pathway.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/28x9kcqt41fkz",
  "venue": "Stem cells international",
  "versions": []
}