Anti-epileptic drug topiramate upregulates TGFβ1 and SOX9 expression in primary embryonic palatal mesenchyme cells: Implications for teratogenicity

Topiramate is an anti-epileptic drug that commonly prescribed not just to prevent seizures but also migraine headaches, with over 8 million prescriptions dispensed annually. use during pregnancy has been linked significantly increased risk of babies born orofacial clefts (OFCs). However, the exact molecular mechanism topiramate teratogenicity unknown. In this study, we first used unbiased antibody array analysis test effect on human embryonic palatal mesenchyme (HEPM) cells. This identified 40 differentially expressed proteins, showing strong connectivity known genes associated clefts. among OFC genes, only TGFβ1 was upregulated in analysis. Next, validated could increase expression and downstream target phospho-SMAD2 primary mouse (MEPM) Furthermore, showed treatment MEPM cells SOX9. SOX9 overexpression chondrocytes cause cleft palate mouse. We propose mediates upregulation signaling through activation γ-aminobutyric acid (GABA) receptors palate. play critical roles morphogenesis, their abnormal provides a plausible etiologic for teratogenic effects topiramate.