ArticlePloS one2021
Anti-epileptic drug topiramate upregulates TGFβ1 and SOX9 expression in primary embryonic palatal mesenchyme cells: Implications for teratogenicity.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Preconception and Early Pregnancy Exposure to Ambient Air Pollution and Risk of Cleft Lip and/or Palate: A Case-Control Study Using Single-Pollutant, Multi-Pollutant, and Mixture-Based Analyses.Birth defects research · 2026Article
- A Comprehensive Review of the Genetic Etiology and Management of Orofacial Clefts.Pediatric discovery · 2026Review
- Clinical case of a pregnant woman with arteriovenous malformation, hemorrhagic venous infarcts and epileptic seizures: a case report.Journal of medical case reports · 2026Article
- MicroRNAs as Epigenetic Biomarkers of Pathogenetic Mechanisms of the Metabolic Syndrome Induced by Antiseizure Medications: Systematic Review.Journal of clinical medicine · 2025Review
- Mechanisms of neurodevelopmental toxicity of topiramate.Critical reviews in toxicology · 2024Review
- An improved multicellular human organoid model for the study of chemical effects on palatal fusion.Birth defects research · 2023Article
- A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity.Adolescent health, medicine and therapeutics · 2023Review
- Isolation and Time-Lapse Imaging of Primary Mouse Embryonic Palatal Mesenchyme Cells to Analyze Collective Movement Attributes.Journal of visualized experiments : JoVE · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Topiramate is an anti-epileptic drug that is commonly prescribed not just to prevent seizures but also migraine headaches, with over 8 million prescriptions dispensed annually. Topiramate use during pregnancy has been linked to significantly increased risk of babies born with orofacial clefts (OFCs). However, the exact molecular mechanism of topiramate teratogenicity is unknown. In this study, we first used an unbiased antibody array analysis to test the effect of topiramate on human embryonic palatal mesenchyme (HEPM) cells. This analysis identified 40 differentially expressed proteins, showing strong connectivity to known genes associated with orofacial clefts. However, among known OFC genes, only TGFβ1 was significantly upregulated in the antibody array analysis. Next, we validated that topiramate could increase expression of TGFβ1 and of downstream target phospho-SMAD2 in primary mouse embryonic palatal mesenchyme (MEPM) cells. Furthermore, we showed that topiramate treatment of primary MEPM cells increased expression of SOX9. SOX9 overexpression in chondrocytes is known to cause cleft palate in mouse. We propose that topiramate mediates upregulation of TGFβ1 signaling through activation of γ-aminobutyric acid (GABA) receptors in the palate. TGFβ1 and SOX9 play critical roles in orofacial morphogenesis, and their abnormal overexpression provides a plausible etiologic molecular mechanism for the teratogenic effects of topiramate.
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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.