Maternal depression disrupts offspring tooth development via suppression of the Wnt/b-catenin pathway
of maternal depression on offspring dental development, a potential effect that remains underexplored despite its established role in impairing neurodevelopment.Materials and methods: A maternal depression model was established in Sprague-Dawley rats via sustained reserpine administration. Maternal phenotypes were validated through behavioral tests and neuroendocrine profiling. Offspring dental tissues were analyzed using single-cell RNA sequencing, bulk RNA sequencing, and molecular assays. Enamel structure and mineralization were assessed by micro-CT, SEM, and hardness testing. The functional role of elevated glucocorticoids was investigated in vitro using ectomesenchymal stem cells (EMSCs).Results: Reserpine-induced maternal depression led to significant offspring enamel defects, including hypomineralization, reduced density, and disorganized microstructure. Transcriptomic profiling of dental tissues identified a marked suppression of the Wnt/b-catenin signaling pathway, which was corroborated by the downregulation of key pathway components (Ctnnb1, Ror2) and enamel matrix proteins (AMELX, AMBN, DSPP) at both mRNA and protein levels. In vitro, corticosterone treatment inhibited EMSCs proliferation and odontogenic differentiation, mirroring the molecular perturbations observed in vivo.Conclusions: This study demonstrates that maternal depression disrupts offspring tooth development. Our integrated data suggest that glucocorticoid excess impairs odontogenesis by suppressing the Wnt/b-catenin signaling pathway, establishing a novel mechanistic link between maternal mental health and developmental dental defects.Clinical relevance: This study identifies maternal depression as a novel, modifiable risk factor for offspring enamel defects. It highlights the need for prenatal mental health screening and early dental assessment in high-risk children to enable prevention.