{
  "abstract": "Inflammation-mediated preeclampsia (I-PE) is associated with increased placental NAD+-dependent ADP-ribosylation and NAD+ depletion. We investigated whether PARP1/2- or tankyrase-sensitive ADP-ribosylation contributes to inflammation-associated trophoblast dysfunction and whether pharmacological inhibition improves trophoblast function under inflammatory stress. We profiled mRNA expression of genes encoding enzymes that catalyze poly-ADP-ribosylation (PARP1, PARP2, TNKS1, TNKS2) and selected enzymes that catalyze mono-ADP-ribosylation (PARP7, PARP10, PARP12, and PARP14), in human I-PE placentas (control n=23; I-PE n=10) and an LPS-induced rat model of I-PE (control n=8, LPS n=8). HTR-8/SVneo cells were treated with TNF- alone or with olaparib, (PARP1/2 inhibitor) or XAV939 (TNKS1/2 inhibitor). Global mono- and poly-ADP-ribosylation (MAR/PAR), including a PARP1-associated ~120-kDa ADP-ribosylation signal and pathway enrichment of proteins identified from this region, were assessed alongside mitochondrial respiration, OXPHOS protein abundance, 4-hydroxynonenal, migration, and viability. In human I-PE placentas, mRNA abundance of poly-ADP-ribosylating enzymes did not differ significantly from controls, whereas mono-ADP-ribosylating enzymes were increased in LPS-exposed rat placentas. In HTR-8/SVneo cells, TNF- induced a prominent PARP1 associated ~120-kDa MAR/PAR signal that was suppressed by olaparib, but not XAV939. Proteins identified from this ~120-kDa region were enriched for known PARP1 targets and immune/stress-response pathways. Olaparib, but not XAV939, improved basal and maximal respiration, ATP production, and spare respiratory capacity. TNF- did not significantly alter oxidative phosphorylation (OXPHOS) subunits, 4-HNE abundance, viability, or migration at 24 h. These data support PARP1/2-sensitive ADP-ribosylation, most consistent with PARP1-linked activity, as a contributor to inflammation-mediated trophoblast bioenergetic dysfunction. The PARP1/2-NAD+ axis may therefore represent a mechanism-directed target for future studies of I-PE.",
  "abstract_shown": true,
  "affiliations": [
    "University of Ottawa"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "A. Nik-Akhtar"
    },
    {
      "name": "S. Vanegas Pineda"
    },
    {
      "name": "J. Ouellet"
    },
    {
      "name": "Y. Cariaco"
    },
    {
      "name": "F. Jahan"
    },
    {
      "name": "K. J. Menzies"
    },
    {
      "affs": [
        0
      ],
      "name": "S. A. Bainbridge"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6j2mg6ynnbp8y.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.20.758860",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.758860v1.full",
  "id": "6j2mg6ynnbp8y",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.758860v1",
  "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",
      "cell biology"
    ],
    [
      "openalex",
      "2729|Pregnancy and preeclampsia studies"
    ]
  ],
  "openalex": "W7223150282",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.758860v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6j2mg6ynnbp8y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:56Z",
      "native_id": "10.64898/2026.10.20.758860",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.20.758860v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "PARP1/2-linked ADP-ribosylation impairs trophoblast mitochondrial respiration in a TNF-α model of inflammation-mediated preeclampsia.",
  "title_text": "PARP1/2-linked ADP-ribosylation impairs trophoblast mitochondrial respiration in a TNF-α model of inflammation-mediated preeclampsia.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:56Z",
  "url": "https://research.draconitic.com/paper/6j2mg6ynnbp8y",
  "venue": "bioRxiv",
  "versions": []
}