{
  "abstract": "Background: Placental foetal vascular malperfusion (PFVM) is a chronic disorder characterised by impaired blood flow and abnormal vascular development, inducing adverse neonatal outcomes. Long chain polyunsaturated fatty acids (LC-PUFAs) play a crucial role in placenta health. We aimed to explore the role of genetic variation in LC-PUFA metabolism in PFVM risk as well as underlying mechanisms.\n\nMethods: Associations were examined between two functional polymorphisms (rs174538 and rs174556) of the fatty acid desaturase 1 (FADS1) gene encoding the rate-limiting enzyme for LC-PUFA metabolism and PFVM among pregnant women (n = 646). Placental transcriptomes were correlated with PFVM and FADS1 genotypes. Various assays were performed in human umbilical vein endothelial cells and trophoblasts with FADS1 inhibitor and LC-PUFA interventions to characterise their function changes.\n\nFindings: Low-function alleles of both polymorphisms were significantly associated with increased PFVM risk and decreased placental FADS1 transcription level. In placenta tissue, lower FADS1 expression is also associated with PFVM. PFVM-associated genes are enriched to pathways related to immune responses, apoptosis, and angiogenesis, which overlap with the genes and pathways associated with the risk alleles and demonstrate a cell-type enrichment to endothelial cells. In vitro, FADS1 inhibition impairs multiple functions of and interactions between endothelial and trophoblast cells. These impairments are reversed by LC-PUFA supplementation.\n\nInterpretation: These findings highlight the impact of maternal LC-PUFA homoeostasis in placenta health and suggest that maternal FADS1 variants can potentially be an early diagnostic marker for PFVM. Our data supports PUFA metabolism as a precision therapeutic or preventive target to reduce placental dysfunction risk.\n\nFunding: 10.13039/100000052NIH, 10.13039/100006710Wayne State University and 10.13039/100006534Michigan State University.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "Zhenjie Liu",
      "orcid": "0000-0002-0878-4052"
    },
    {
      "name": "Ze Long"
    },
    {
      "name": "Stephanie Nartey"
    },
    {
      "name": "Li Tao"
    },
    {
      "name": "Shahrazad Saab",
      "orcid": "0000-0002-2093-5511"
    },
    {
      "name": "Robert Ty Partridge",
      "orcid": "0000-0002-2905-4737"
    },
    {
      "name": "Carolyn M. Salafia"
    },
    {
      "name": "Zheyun Peng"
    },
    {
      "name": "Yang Jiang"
    },
    {
      "name": "Tengfei Ma"
    },
    {
      "name": "Douglas Ruden"
    },
    {
      "name": "Nigel Paneth"
    },
    {
      "name": "Jean M. Kerver"
    },
    {
      "name": "Raina Nakova Fichorova"
    },
    {
      "name": "Wanqing Liu",
      "orcid": "0000-0001-7727-6900"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6965mkyjgsh0c.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ebiom.2026.106517",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696122/",
  "id": "6965mkyjgsh0c",
  "issns": [
    "2352-3964"
  ],
  "landing_url": "https://doi.org/10.1016/j.ebiom.2026.106517",
  "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",
      "Articles"
    ],
    [
      "openalex",
      "2729|Pregnancy and preeclampsia studies"
    ]
  ],
  "openalex": "W7222801399",
  "pdf_url": "https://europepmc.org/articles/PMC13696122?pdf=render",
  "pmcid": "PMC13696122",
  "pmid": "42892213",
  "published": "2026-10-17",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/6965mkyjgsh0c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:32Z",
      "native_id": "PMC13696122",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.ebiom.2026.106517"
    },
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42892213",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42892213"
    },
    {
      "first_seen": "2026-10-30T12:19:49Z",
      "native_id": "10.1016/j.ebiom.2026.106517",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2352396426004019"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Pregnancy and preeclampsia studies",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Decreased function of fatty acid desaturase 1 is associated with placental foetal vascular malperfusion and highlights the key role of the maternal–foetal interface",
  "title_text": "Decreased function of fatty acid desaturase 1 is associated with placental foetal vascular malperfusion and highlights the key role of the maternal–foetal interface",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:31Z",
  "url": "https://research.draconitic.com/paper/6965mkyjgsh0c",
  "venue": "eBioMedicine",
  "versions": []
}