Mo Jiali, Zuo Jingye, Yu Lin, Zhang Huishan, Weng Shuting, Ye Leping
Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China.
Department of Respiratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Arch Toxicol. 2025 Mar 24. doi: 10.1007/s00204-025-04014-2.
Perfluorooctane sulfonate (PFOS), a widely persistent environmental pollutant, has been demonstrated to disrupt lung development in animal models. However, its cellular and molecular mechanisms remain insufficiently understood. This study examines the effects of prenatal PFOS exposure on lung development and function in offspring rats. Pregnant rats were exposed to PFOS at concentrations relevant to both environmental and occupational exposures, with doses of 0, 0.01, 0.1, and 1 mg/kg/day from gestational day 11-20. We primarily evaluated morphological changes, pulmonary function, bronchoalveolar lavage fluid composition, and alterations in trace element and fatty acid metabolism at postnatal days 0, 4, 14, 21, and 60. Single-cell RNA sequencing was employed to profile cellular and molecular responses in the lungs. Our results show that PFOS exposure leads to dose-dependent reductions in alveolar development, increased pulmonary injury, fibrosis, and impaired lung function. PFOS also changes lung cell composition, particularly affecting structural and immune cells, and shifts immune responses from innate to adaptive immunity. Differential gene expression analyses revealed the upregulation of Fam111a and downregulation of Stk35, implicating these genes in PFOS-induced lung injury and repair processes. In addition, pathway analyses demonstrated suppression of immune-related signaling pathways and disruption of cell adhesion and phagocytosis, which may exacerbate lung tissue injury. These findings provide novel insights into the developmental toxicity of PFOS and highlight its potential long-term health risks.
全氟辛烷磺酸（PFOS）是一种广泛存在且持久的环境污染物，已被证明会破坏动物模型中的肺发育。然而，其细胞和分子机制仍未得到充分了解。本研究考察了产前暴露于PFOS对仔鼠肺发育和功能的影响。将怀孕大鼠暴露于与环境和职业暴露相关浓度的PFOS中，从妊娠第11天至20天，剂量分别为0、0.01、0.1和1毫克/千克/天。我们主要评估了出生后第0、4、14、21和60天的形态变化、肺功能、支气管肺泡灌洗液成分以及微量元素和脂肪酸代谢的改变。采用单细胞RNA测序来分析肺中的细胞和分子反应。我们的结果表明，PFOS暴露导致肺泡发育呈剂量依赖性减少、肺损伤增加、纤维化以及肺功能受损。PFOS还会改变肺细胞组成，尤其影响结构和免疫细胞，并将免疫反应从先天免疫转变为适应性免疫。差异基因表达分析显示Fam111a上调和Stk35下调，表明这些基因参与了PFOS诱导的肺损伤和修复过程。此外，通路分析表明免疫相关信号通路受到抑制，细胞黏附和吞噬作用受到破坏，这可能会加剧肺组织损伤。这些发现为PFOS的发育毒性提供了新的见解，并突出了其潜在的长期健康风险。
