{
  "abstract": "During pregnancy, placenta-derived proteins such as pregnancy-specific glycoprotein 1 (PSG1) enter the maternal circulation, providing a window into placental health and enabling liquid biopsy strategies for monitoring pregnancy disorders. PSG1, a highly glycosylated protein secreted by syncytiotrophoblast (STB) cells, reflects trophoblast differentiation status. Circulating PSG1 levels are reduced in early-onset preeclampsia (PE), but how PSG1 glycosylation is altered in this condition remains unclear. Here, we show by liquid chromatography-tandem mass spectrometry that native PSG1 purified from healthy and early-onset PE pregnancies carries an O-linked glycan in its N domain in addition to diverse N-linked glycans. In PE, PSG1 N-glycans displayed a shift toward increased oligomannose structures and reduced sialylation. Induction of endoplasmic reticulum (ER) stress in primary STBs altered the glycosylation enzyme machinery, and single-nucleus transcriptomic data indicated a reduced contribution of mature STB populations in PE, consistent with an immature STB-like glycoprotein signature. Altered N-glycosylation increased binding to mannose and asialoglycoprotein receptors and cellular uptake, suggesting enhanced hepatic clearance as a possible explanation for reduced circulating PSG1 levels in PE. Our data link ER stress during STB differentiation to altered glycoprotein maturation and identify PSG1 glycosylation as a readout of a stress-impaired STB in PE. Glycan features of circulating placental proteins could therefore provide information beyond protein levels alone and complement liquid biopsy approaches.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.",
    "Glyco-HAM, a Cooperation of Universität Hamburg, Technology Platform Mass Spectrometry and University Medical Center Hamburg-Eppendorf, Hamburg, Germany.",
    "Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20817, USA.",
    "Global Development CMC Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an Der Riss, Germany.",
    "3D Tissue Bioprinting Laboratory, National Center for Advancing Translational Sciences, National Institute of Sciences, Bethesda, MD, USA.",
    "Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada.",
    "Ottawa Institute of Systems Biology, Ottawa, ON, Canada.",
    "Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany.",
    "Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.",
    "Department of Obstetrics and Gynecology, School of Medicine, Semmelweis University, Budapest, Hungary.",
    "Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary.",
    "Genesis Theranostix Group, Budapest, Hungary.",
    "Experimental and Clinical Research Center, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany.",
    "Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.",
    "Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20817, USA. gabriela.dveksler@usuhs.edu.",
    "Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. s.blois@uke.de.",
    "Glyco-HAM, a Cooperation of Universität Hamburg, Technology Platform Mass Spectrometry and University Medical Center Hamburg-Eppendorf, Hamburg, Germany. s.blois@uke.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Charlotte Harms"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiru Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "James Warren"
    },
    {
      "affs": [
        3
      ],
      "name": "Julia Baumeister"
    },
    {
      "affs": [
        3
      ],
      "name": "Fabian Higel"
    },
    {
      "affs": [
        4
      ],
      "name": "Cristina Antich"
    },
    {
      "affs": [
        4
      ],
      "name": "Marc Ferrer"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Jennifer J Hill"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariana G Garcia"
    },
    {
      "affs": [
        7
      ],
      "name": "Alexandra Gellhaus"
    },
    {
      "affs": [
        8,
        9,
        10,
        11
      ],
      "name": "Nándor Gábor Than"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Florian Herse"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefan Verlohren"
    },
    {
      "affs": [
        14
      ],
      "name": "Gabriela S Dveksler"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Sandra M Blois",
      "orcid": "0000-0002-0434-2660"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fr83hf5362xy1.bib",
  "cited_by": 0,
  "doi": "10.1186/s43556-026-00634-x",
  "fulltext_url": "https://doi.org/10.1186/s43556-026-00634-x",
  "id": "fr83hf5362xy1",
  "issns": [
    "2662-8651"
  ],
  "landing_url": "https://doi.org/10.1186/s43556-026-00634-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
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    [
      "openalex",
      "2729|Pregnancy and preeclampsia studies"
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  "pdf_url": "https://link.springer.com/content/pdf/10.1186/s43556-026-00634-x.pdf",
  "pmcid": "PMC13722672",
  "pmid": "42961606",
  "published": "2026-10-01",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/fr83hf5362xy1.ris",
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      "first_seen": "2026-11-01T14:21:16Z",
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      "url": "https://europepmc.org/article/MED/42961606"
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    {
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Pregnancy and preeclampsia studies",
      "subfield": "reproductive-child"
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  ],
  "title": "Syncytiotrophoblast differentiation defects drive ER stress and reprogram placental PSG1 glycosylation in preeclampsia",
  "title_text": "Syncytiotrophoblast differentiation defects drive ER stress and reprogram placental PSG1 glycosylation in preeclampsia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:27Z",
  "url": "https://research.draconitic.com/paper/fr83hf5362xy1",
  "venue": "Molecular Biomedicine",
  "versions": []
}