Trial reportProceedings of the National Academy of Sciences of the United States of America2014
GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Investigating the Role of Skin Autofluorescence in Gestational Diabetes Mellitus: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Discrepancy in Insulin Regulation between Gestational Diabetes Mellitus (GDM) Platelets and Placenta.The Journal of biological chemistry · 2016Trial
- Serum Serotonin Levels and Postpartum Depression in Women with Gestational Diabetes Mellitus: A Prospective Psychobiological Study.Journal of clinical medicine · 2026Article
- The placental tryptophan pathway across gestation: implications for pregnancy outcomes.Human reproduction update · 2026Review
- Placental expression of the serotonin transporter (SERT) gene: associations with maternal overweight/obesity and neonatal anthropometry.International journal of obesity (2005) · 2026Article
- Effects of selective serotonin reuptake inhibitors on the placenta†.Biology of reproduction · 2025Review
- Gestational diabetes mellitus and development of intergenerational non-alcoholic fatty liver disease (NAFLD) after delivery: a systematic review and meta-analysis.EClinicalMedicine · 2024Article
- Serotonin Transporter-dependent Histone Serotonylation in Placenta Contributes to the Neurodevelopmental Transcriptome.Journal of molecular biology · 2024Article
- Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome.bioRxiv : the preprint server for biology · 2023Article
- Glucose, Insulin and Oxygen Modulate Expression of Serotonin-Regulating Genes in Human First-Trimester Trophoblast Cell Line ACH-3P.Biomedicines · 2023Article
- Identification of the Active Compound of Liu Wei Di Huang Wan for Treatment of Gestational Diabetes Mellitus via Network Pharmacology and Molecular Docking.Journal of diabetes research · 2022Article
- Research progress of placental vascular pathophysiological changes in pregnancy-induced hypertension and gestational diabetes mellitus.Frontiers in physiology · 2022Review
- Serotonin system in the human placenta - the knowns and unknowns.Frontiers in endocrinology · 2022Review
- Differential Serotonin Uptake Mechanisms at the Human Maternal-Fetal Interface.International journal of molecular sciences · 2021Article
- The placenta-brain-axis.Journal of neuroscience research · 2021Review
- Frontiers of Serotonin Beyond the Brain.Pharmacological research · 2019Article
- Association with serotonin transporter enables the phosphorylation of insulin receptor in placenta.Current topics in biochemical research · 2019Article
- Epigenetic Profiles Reveal That ADCYAP1 Serves as Key Molecule in Gestational Diabetes Mellitus.Computational and mathematical methods in medicine · 2019Article
- Polysaccharide IV fromFrontiers in endocrinology · 2018Article
- Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway.Journal of cellular physiology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Serotonin (5-HT) transporter (SERT) regulates the level of 5-HT in placenta. Initially, we found that in gestational diabetes mellitus (GDM), whereas free plasma 5-HT levels were elevated, the 5-HT uptake rates of trophoblast were significantly down-regulated, due to impairment in the translocation of SERT molecules to the cell surface. We sought to determine the factors mediating the down-regulation of SERT in GDM trophoblast. We previously reported that an endoplasmic reticulum chaperone, ERp44, binds to Cys200 and Cys209 residues of SERT to build a disulfide bond. Following this posttranslational modification, before trafficking to the plasma membrane, SERT must be dissociated from ERp44; and this process is facilitated by insulin signaling and reversed by the insulin receptor blocker AGL2263. However, the GDM-associated defect in insulin signaling hampers the dissociation of ERp44 from SERT. Furthermore, whereas ERp44 constitutively occupies Cys200/Cys209 residues, one of the SERT glycosylation sites, Asp208 located between the two Cys residues, cannot undergo proper glycosylation, which plays an important role in the uptake efficiency of SERT. Herein, we show that the decrease in 5-HT uptake rates of GDM trophoblast is the consequence of defective insulin signaling, which entraps SERT with ERp44 and impairs its glycosylation. In this regard, restoring the normal expression of SERT on the trophoblast surface may represent a novel approach to alleviating some GDM-associated complications.
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