Short- and long-term effects of early-life exposure to PFOS or its alternative PFBS on pulmonary development

Accumulating evidence suggests that maternal exposure to per- and polyfluoroalkyl substances during pregnancy is associated with adverse outcomes in offspring. As a short-chain alternative to perfluorooctane sulfonate (PFOS), the impacts of perfluorobutane sulfonate (PFBS) on pulmonary development across the lifespan remain unclear. Herein, pregnant BALB/c mice were provided drinking water containing 10 μg/L PFBS, 500 μg/L PFBS, or 500 μg/L PFOS from gestation through lactation. Significant bioaccumulation of PFBS was identified in fetal organs. On postnatal day 1 (PND 1), offspring prenatally exposed to PFOS or PFBS exhibited simplified alveolar structures, decreased surfactant protein C levels, and impaired angiogenesis. The expression of Vegfα, an angiogenesis-related gene, was downregulated in the high-dose exposure groups, with a corresponding reduction in VEGFA protein levels. Meanwhile, Ocln, Cldn1, and Occludin were significantly decreased, indicating disrupted pulmonary barrier function. These alterations were reversed by PND 21. Furthermore, under ovalbumin challenge, all exposed adult offspring exhibited increased allergic susceptibility, characterized by enhanced pulmonary inflammatory infiltration, elevated bronchial mucin secretion, reduced Occludin protein levels, and upregulated Th2-type inflammatory cytokines (including IL-4, IL-5, and IL-13). RNA-seq analysis revealed that exposure to both PFBS and PFOS impaired the expression of genes critical for pulmonary development. Overall, our study indicates that perinatal exposure to PFOS or PFBS leads to both short- and long-term adverse effects on pulmonary development, suggesting that PFBS is not a safe alternative to PFOS.