Benzo[a]pyrene exposure affect the formation of dental hard tissue via the regulation of glycerophospholipid metabolism

The formation of enamel occurs across multiple developmental stages and is highly sensitive to disruptions in cellular signaling. Perinatal complications, preterm birth, and exposure to environmental chemicals are systemic factors known to contribute to developmental defects of enamel (DDE). These defects adversely affect normal oral physiological function and impact patients’ daily lives. The precise pathophysiology of DDE, however, remains unclear, complicating efforts at prevention. Consequently, elucidating the mechanisms through which environmental exposures lead to DDE is essential for developing preventive and early intervention strategies to support lifelong oral health. Sprague Dawley (SD) rats received daily intraperitoneal injections of 5 µg/kg benzo[a]pyrene (B[a]P) from postnatal day 1 to day 42 to establish the DDE model. At postnatal week 6, we performed phenotypic analysis using dual-platform untargeted metabolomics, transcriptomics sequencing, hematological examination, and micro-CT. Statistical evaluation of all data employed Student’s t-tests or one-way ANOVA with Tukey’s post hoc test (P < 0.05). B[a]P exposure shortened molar crowns and induced abnormal pits on the lingual side of incisors, indicating disrupted tooth development through micro-CT analysis. It also reduced incisor enamel volume and density, leading to a DDE phenotype. This enamel defect coincided with hepatic metabolic disorders and an upregulation of phospholipid metabolism. Throughout DDE progression, differentially enriched metabolites within phospholipid pathways were observed in dental epithelial cells concurrently with reduced transcriptional levels of enamel formation genes. This study established a rat model of DDE and demonstrated the multifaceted impacts of B[a]P exposure on both tooth development and systemic metabolism, revealing a correlation between altered phospholipid metabolism and transcriptional changes in enamel formation-related genes. These findings provide the first evidence linking glycerophospholipid metabolism to exposure-induced DDE and suggest its potential relevance for DDE prevention. This work provides further theoretical support for promoting oral health management in early childhood.