Cetylpyridinium chloride disrupts maternal-to-zygotic transition during early embryonic development by impairing...

Cetylpyridinium chloride (CPC), a widely utilized quaternary ammonium compound, serves as both an antiseptic and antibacterial agent. Previous studies have highlighted its toxic effects across various cell types, including reproductive toxicity. However, the specific impacts of CPC on female reproduction, particularly on early embryonic development, as well as the underlying mechanisms, remain incompletely understood. In this study, we revealed that environmental concentrations of CPC exposure influenced mouse early embryonic development in vitro in a dose-dependent manner. Transcriptomic sequencing identified 3799 differentially expressed genes (DEGs), suggesting that CPC exposure disrupted gene expression in 2-cell embryos. Functional enrichment analysis further revealed that DEGs were significantly involved in pathways and processes related to mitochondrial function, ROS, and gene transcription. In-depth analysis revealed that CPC exposure impeded zygotic genome activation and degradation of maternal effect genes, thereby disrupting the maternal-to-zygotic transition (MZT). Further investigations demonstrated that CPC exposure reduced ATP levels in 2-cell embryos, elevated mitochondrial membrane potential, markedly increased ROS and DHE levels, and heightened DNA damage, indicating mitochondrial dysfunction and oxidative stress. Moreover, CPC exposure altered histone methylation and acetylation modification patterns, marked by elevated levels of H3K9me3 and acH3K27, and decreased levels of H3K27me3 and acH3K9. Overall, CPC exposure below environmental concentrations disrupts MZT by impairing mitochondrial function and histone modifications, ultimately leading to developmental arrest in mouse preimplantation embryos. These findings highlight the potential reproductive toxicity of CPC on female health.