ArticleiScience2023
Perturbation of placental protein glycosylation by endoplasmic reticulum stress promotes maladaptation of maternal hepatic glucose metabolism.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- The dynamics of glycosylation in trophoblast cells: development, function, and pregnancy-related disorders.Annals of medicine · 2026Review
- Chondroitin sulfate shapes the unfolded protein response in osteosarcoma to sustain cancer cell survival during ER stress.Cell death & disease · 2026Article
- Abnormal Galectin Signaling in the Pathomechanisms of Placental Dysfunction in Gestational Diabetes Mellitus.International journal of molecular sciences · 2026Review
- Review
- Association of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation.Environment international · 2025Article
- Navigating Cellular Stress: Endoplasmic Reticulum Stress and the Unfolded Protein Response in the Molecular Pathogenesis of Preeclampsia.Cell biochemistry and biophysics · 2025Review
- Multi-omic insights of preeclampsia and cardiovascular health outcomes.Communications medicine · 2025Review
- Endoplasmic reticulum stress: an emerging therapeutic target for preeclampsia†.Biology of reproduction · 2025Review
- Proteomic analysis of hydrogen peroxide-treated human chondrocytes shows endoplasmic reticulum stress, cytoskeleton remodeling, and altered secretome composition.Cell communication and signaling : CCS · 2025Article
- Spatial metabolomics and transcriptomics reveal cell type-specific dynamics in the placenta of patients with late-onset preeclampsia.Frontiers in cell and developmental biology · 2025Article
- Exercise therapy for gestational diabetes mellitus: from basic to clinical.Frontiers in medicine · 2025Review
- Current investigation of carcinoembryonic antigen cell adhesion molecule (CEACAM) biology summary of the 32nd CEA symposium: 20-23 September 2024. Würzburg, Germany.European journal of clinical investigation · 2024Article
- iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation.iScience · 2024Article
- A stress paradox: the dual role of the unfolded protein response in the placenta.Frontiers in endocrinology · 2024Review
- Placenta: an old organ with new functions.Frontiers in immunology · 2024Review
- CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns.Cell communication and signaling : CCS · 2023Article
- Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity. ER stress alters the expression of 66 of the 146 genes annotated with "protein glycosylation" and reduces the expression of sialyltransferases. Using mouse placental explants, we show ER stress promotes the secretion of mis-glycosylated glycoproteins. Pregnant mice carrying placentas with junctional zone-specific ER stress have reduced blood glucose, anomalous hepatic glucose metabolism, increased cellular stress and elevated DNA methyltransferase 3A. Using pregnancy-specific glycoproteins as a readout, we also demonstrate aberrant glycosylation of placental proteins in women with ePE, thus providing a mechanistic link between ePE and subsequent maternal metabolic disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.