New insights into the effects of PFOS exposure on rat lung development: morphological, functional, and single-cell sequencing analysis

Abstract

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.