{
  "abstract": "Excessive left ventricular trabeculation and thinning of the compacted myocardium arise during cardiac development and may be accompanied by myocardial dysfunction. Gestational exposure to all-trans retinoic acid (ATRA) induces a comparable phenotype in mice, providing a model for evaluating prenatal pharmacological intervention. We examined whether 3i-0777, a small-molecule enhancer of GATA4-NKX2-5 transcriptional synergy, could attenuate these structural and functional abnormalities. Pregnant C57BL/6NCrl dams were randomly assigned to untreated control, vehicle control, ATRA, or ATRA plus 3i-0777 groups (12 independent litters per group). Both ATRA-exposed groups received ATRA (50 mg/kg) on embryonic day (E)12.5. In the ATRA plus 3i-0777 group, 3i-0777 (15 mg/kg) was administered as a separate injection concurrently with ATRA at E12.5, followed by 5 mg/kg every 8 h (three doses per day) on E13.5-E15.5. At postnatal day 1, one pup was randomly selected from each litter for echocardiography and subsequent histomorphometry. The echocardiographic and histomorphometric ratios of non-compacted to compacted myocardial layer thickness (N/C ratios) were higher, and the absolute magnitude of global longitudinal strain (|GLS|) was lower, in the ATRA group than in either control group (all adjusted P < 0.001). Compared with the ATRA group, the ATRA plus 3i-0777 group had lower echocardiographic and histomorphometric N/C ratios (0.58 {+/-} 0.19 vs 2.19 {+/-} 0.18 and 0.90 {+/-} 0.33 vs 2.46 {+/-} 0.48, respectively), higher |GLS| (25.9 {+/-} 2.5% vs 15.3 {+/-} 2.7%), and a smaller left ventricular internal diameter at end-diastole (1.15 {+/-} 0.06 vs 1.42 {+/-} 0.10 mm; all adjusted P < 0.001). These findings provide proof of concept that ATRA-induced left ventricular hypertrabeculation and dysfunction can be pharmacologically attenuated in utero.",
  "abstract_shown": true,
  "affiliations": [
    "Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Q. Shu"
    },
    {
      "name": "Z. Wang"
    },
    {
      "name": "Q. Meng"
    },
    {
      "name": "X. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Yin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e8hgq45c212sm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.03.748426",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.748426v1.full",
  "id": "e8hgq45c212sm",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.748426v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "developmental biology"
    ],
    [
      "openalex",
      "1312|Congenital heart defects research"
    ]
  ],
  "openalex": "W7211870551",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.748426v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e8hgq45c212sm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:55Z",
      "native_id": "10.64898/2026.09.03.748426",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.03.748426v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:developmental biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "Prenatal 3i-0777 treatment attenuates left ventricular hypertrabeculation and dysfunction in a retinoic acid-induced mouse model",
  "title_text": "Prenatal 3i-0777 treatment attenuates left ventricular hypertrabeculation and dysfunction in a retinoic acid-induced mouse model",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:55Z",
  "url": "https://research.draconitic.com/paper/e8hgq45c212sm",
  "venue": "bioRxiv",
  "versions": []
}