{
  "abstract": "Reproductive aging is associated with reduced fertility and increased risk of adverse pregnancy outcomes, including miscarriage, placental dysfunction, and fetal growth restriction. While age-related decline in oocyte quality contributes to early pregnancy loss, uterine dysfunction is recognized as a critical determinant of pregnancy success, particularly for complications arising after implantation of blastocysts. However, the mechanisms by which uterine aging impairs post-implantation blastocyst development remain unclear. We tested the hypothesis that reproductive aging limits decidual growth through impaired progesterone (P4) responsiveness and fibrotic remodeling. An artificial decidualization model with young and aged virgin mice was used to isolate uterine-specific effects independent of ovarian and embryonic factors. The results indicate that reproductive aging markedly reduced decidual expansion. Aged decidualized uteri exhibited impaired progesterone receptor (PGR) expression and spatial dysregulation and reduced expression of P4-responsive genes. Transcriptomic profiling of decidualized uteri revealed coordinated suppression of stromal differentiation, cell-cycle, growth-factor, and extracellular matrix (ECM)-remodeling programs together with broader changes in stress, immune, and metabolic pathways. Primary stromal cells from aged uteri showed reduced proliferative capacity and attenuated induction of decidualization-associated genes. Histological analyses demonstrated increased accumulation of fibrillar Type I and III collagens and impaired ECM remodeling. These findings provide an integrated molecular, cellular, and structural framework linking impaired P4 responsiveness, stromal dysfunction, and fibrotic remodeling to reduced decidual growth during reproductive aging.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s44494-026-00007-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Animal Science, North Carolina State University, Raleigh, NC 27695-7621 USA",
    "Epigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA",
    "Department of Molecular Biomedical Sciences and Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27607 USA",
    "The Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27695-7621 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Magdalina J. Cummings"
    },
    {
      "affs": [
        0
      ],
      "name": "Bangmin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Sudikshya Paudel"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiukun Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Skye Sgouridis"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinxia Peng"
    },
    {
      "affs": [
        1
      ],
      "name": "Guang Hu"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Xiaoqiu Wang",
      "orcid": "0000-0001-9660-528X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/av8288b76snq3.bib",
  "cited_by": 0,
  "doi": "10.1186/s44494-026-00007-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696648/",
  "id": "av8288b76snq3",
  "issns": [
    "3091-3276"
  ],
  "landing_url": "https://doi.org/10.1186/s44494-026-00007-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2403|Reproductive System and Pregnancy"
    ]
  ],
  "openalex": "W7223563749",
  "pdf_url": "https://link.springer.com/content/pdf/10.1186/s44494-026-00007-9.pdf",
  "pmcid": "PMC13696648",
  "pmid": "42935627",
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/av8288b76snq3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "PMC13696648",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s44494-026-00007-9"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Reproductive System and Pregnancy",
      "subfield": "immunology"
    }
  ],
  "title": "Uterine function and reproduction aging. I. Molecular and structural alterations associated with impaired decidualization in aged mouse uteri",
  "title_text": "Uterine function and reproduction aging. I. Molecular and structural alterations associated with impaired decidualization in aged mouse uteri",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:57Z",
  "url": "https://research.draconitic.com/paper/av8288b76snq3",
  "venue": "Uterine Research",
  "versions": []
}