Single cell RNA sequencing reveals the reshaping effect of perfluorooctanoic acid on the intestinal microenvironment of mice

作者：Ya Gao, Jiayun Guan, Rui Zhou, Z Li, Tianyang Chen, Ke Yang, Rong Huang, Yue Huang, Siting Zheng, Zhenhua Huang, Xiaoxiang Rong · 发表于：Ecotoxicology and Environmental Safety · 年份：2025 · DOI：10.1016/j.ecoenv.2025.118540 · 被引用次数：3 · 研究领域：Per- and polyfluoroalkyl substances research、Air Quality and Health Impacts

Perfluorooctanoic acid (PFOA), a prevalent perfluorinated compound pollutants, has been implicated in the development of various gastrointestinal disorders. However, the specific PFOA-induced intestinal microenvironment alterations remain poorly characterized. In this study, we established a chronic PFOA toxicity model in C57BL/6 mice of both sexes through exposure to PFOA at doses of 0, 1, 5, and 10 mg/kg/day. Single-cell RNA sequencing (scRNA-seq) was performed on the small intestine tissues from female mice, and key findings were validated through flow cytometry and immunohistochemistry. Histopathological analysis revealed that PFOA induced intestinal damage in both sexes, with a more severe impact observed in female mice. scRNA-seq analysis demonstrated that PFOA treatment triggered abnormal proliferation of intestinal epithelial cells, particularly the expansion of Ada high enterocyte cells, suggesting their potential role in injury repair process. Furthermore, PFOA exposure induced significant remodeling of the intestinal immune microenvironment, characterized by decreased overall lymphocyte infiltration, heightened activation of remaining cytotoxic CD8 + T cells, and a notable increase in proliferative CD8 + T cells. A significant reduction in FOXP3 + regulatory T cells further contributed to a pro-inflammatory shift within the T cell population. Cell-cell interaction analysis revealed enhanced macrophage-CD8 + T cell communication via the CCR1-CCL5 axis, suggesting a ...