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| Item Type: | Article |
|---|---|
| Title: | Syncytiotrophoblast differentiation defects drive ER stress and reprogram placental PSG1 glycosylation in preeclampsia |
| Creators: |
Harms, Charlotte, Wang, Yiru, Warren, James, Baumeister, Julia, Higel, Fabian, Antich, Cristina, Ferrer, Marc, Hill, Jennifer J., Garcia, Mariana G., Gellhaus, Alexandra, Than, Nándor Gábor, Herse, Florian  ORCID: https://orcid.org/0000-0002-9305-8134, Verlohren, Stefan ORCID: https://orcid.org/0000-0003-3507-8636, Dveksler, Gabriela S. and Blois, Sandra M. ORCID: https://orcid.org/0000-0002-0434-2660
|
| 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. |
| Keywords: | PSG1, Preeclampsia, STB Differentiation, N-Glycosylation, ER Stress |
| Source: | Molecular Biomedicine |
| ISSN: | 2662-8651 |
| Publisher: | Springer Nature |
| Volume: | 7 |
| Number: | 1 |
| Page Range: | 235 |
| Date: | 30 October 2026 |
| Official Publication: | https://doi.org/10.1186/s43556-026-00634-x |
| PubMed: | View item in PubMed |
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