氯化十六烷基吡啶通过损害线粒体功能和组蛋白修饰，干扰早期胚胎发育过程中的母体至合子过渡

Cetylpyridinium chloride disrupts maternal-to-zygotic transition during early embryonic development by impairing mitochondrial function and histone modification

氯化十六烷基吡啶通过损害线粒体功能和组蛋白修饰，干扰早期胚胎发育过程中的母体至合子过渡

Authors: Caiyun Wu, Zhiming Ding, Xuanxi Li, Yan Xu, Huilei Chen, Hongzhen Ruan, Ping Zhou, Zuying Xu, Huifen Xiang

Source: Ecotoxicology And Environmental Safety

PMID: 40609270

DOI: 10.1016/j.ecoenv.2025.118608

Abstract

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.

Keywords: Cetylpyridinium chloride; Early embryonic development; Histone modification; Maternal-to-zygotic transition; Mitochondria.

摘要

氯己定(CPC）是一种广泛应用的四级胺化合物，兼具抗感染和抗菌作用。先前研究已指出其对多种细胞类型具有毒性作用，包括生殖毒性。然而，CPC对女性生殖系统，尤其是早期胚胎发育的具体影响及其潜在机制仍未完全明了。本研究发现，环境浓度的CPC暴露以剂量依赖性方式影响小鼠体外早期胚胎发育。转录组测序识别出3799个差异表达基因(DEGs），表明CPC暴露扰乱了2细胞期胚胎的基因表达。功能富集分析进一步揭示，DEGs显著参与与线粒体功能、活性氧(ROS）及基因转录相关的通路和过程。深入分析显示，CPC暴露阻碍了合子基因组激活和母体效应基因的降解，从而扰乱了母体到合子的过渡(MZT）。进一步研究表明，CPC暴露降低了2细胞胚胎中的ATP水平，提高了线粒体膜电位，显著增加了ROS和DHE水平，并加剧了DNA损伤，表明线粒体功能障碍和氧化应激。此外，CPC暴露改变了组蛋白甲基化和乙酰化修饰模式，表现为H3K9me3和acH3K27水平升高，以及H3K27me3和acH3K9水平降低。总体而言，低于环境浓度的CPC暴露通过损害线粒体功能和组蛋白修饰扰乱MZT，最终导致小鼠胚胎着床前发育停滞。这些发现突显了CPC对女性健康潜在的生殖毒性。

关键词：十六烷基吡啶氯化物；早期胚胎发育；组蛋白修饰；母体至合子过渡；线粒体