{
  "abstract": "Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous environmental endocrine disruptor, has been detected in over 97% of pregnant women. Epidemiological studies have linked DEHP exposure to increased risk of recurrent pregnancy loss (RPL); however, the underlying mechanistic pathways remain poorly characterized. This study employed an integrated multi-omics approach combining network toxicology, machine learning, Mendelian randomization (MR), single-cell RNA sequencing (scRNA-seq), and molecular dynamics (MD) simulation to elucidate the molecular mechanism by which DEHP exposure induces RPL. Network toxicology analysis identified 143 shared targets between DEHP-associated genes and RPL-related genes, which were significantly enriched in focal adhesion and PI3K-Akt signaling pathways. Integration of machine learning analysis on RPL transcriptomic data with MR identified ITGA2 as a genetically supported protective factor causally associated with RPL. scRNA-seq precisely localized ITGA2 expression to decidual endothelial cells, where it was significantly downregulated in RPL patients. In silico gene knockout predicted that ITGA2 deficiency leads to dysregulation of angiogenesis- and immune regulation-associated genes, impairing decidual endothelial cell function and the immunological microenvironment. MD simulation predicted that DEHP forms a direct, stable complex with the extracellular domain of ITGA2. In HUVECs, DEHP dose-dependently reduced ITGA2 mRNA and protein levels and impaired migration. Silencing ITGA2 reproduced this migration defect, indicating that ITGA2 downregulation contributes to DEHP-induced endothelial dysfunction. Collectively, these findings identify ITGA2 as a biologically and genetically supported candidate linking DEHP exposure to impaired decidual endothelial function in RPL and provide a basis for future biomarker and mechanistic studies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of NICU, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China",
    "Department of Pediatrics, Jiangshan People's Hospital, Quzhou, Zhejiang, China",
    "Department of NICU, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Corresponding authors.",
    "Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Corresponding authors."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhou Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xun Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yujia Luo"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuanyuan Zhou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b4rsqnwvrm3rv.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ecoenv.2026.120960",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S014765132601290X",
  "id": "b4rsqnwvrm3rv",
  "issns": [
    "0147-6513",
    "1090-2414"
  ],
  "landing_url": "https://doi.org/10.1016/j.ecoenv.2026.120960",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "GE1-350"
    ],
    [
      "lcc",
      "TD172-193.5"
    ],
    [
      "openalex",
      "2403|Reproductive System and Pregnancy"
    ]
  ],
  "openalex": "W7223182388",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/b4rsqnwvrm3rv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:31Z",
      "native_id": "335c7d3bd05c4ae395836f6714a02c3d",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.ecoenv.2026.120960"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Reproductive System and Pregnancy",
      "subfield": "immunology"
    }
  ],
  "title": "Multi-omics analysis reveals ITGA2 mediates DEHP-induced decidual endothelial dysfunction in recurrent pregnancy loss",
  "title_text": "Multi-omics analysis reveals ITGA2 mediates DEHP-induced decidual endothelial dysfunction in recurrent pregnancy loss",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:31Z",
  "url": "https://research.draconitic.com/paper/b4rsqnwvrm3rv",
  "venue": "Ecotoxicology and Environmental Safety",
  "versions": []
}