Abstract

As perfluorooctanesulfonate (PFOS) is phased out, its alternative, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), has been widely used in China. However, the health risks associated with F-53B exposure, particularly its potential effects on offspring respiratory outcomes, remain largely unclear. We therefore investigated whether gestational and lactational exposures to PFOS or F-53B alter early lung development and influence asthma susceptibility in offspring. Pregnant mice were exposed to PFOS or F-53B at a dose relevant to the human tolerable daily intake of PFOS during gestation and lactation, and maternal–fetal distribution was quantified by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) at embryonic day 18.5. Both PFOS and F-53B efficiently crossed the placenta and accumulated in the fetal lungs. Following ovalbumin sensitization and challenge, offspring from exposed dams showed increased airway inflammatory pathology and goblet cell hyperplasia, along with higher bronchoalveolar lavage protein and elevated pulmonary Il5 and Il1b expression, with PFOS inducing more pronounced functional changes. Early life exposure downregulated pulmonary tight junction proteins ZO-1 and Occludin at postnatal day 1, while transcriptomics revealed persistent dysregulation of immune-related pathways. 16S rRNA gene sequencing further demonstrated alterations in gut microbiota diversity and composition. Together, these findings suggest that early life exposure to PFOS or F-53B is associated with changes in lung-barrier development, immune signaling, and gut microbial composition, which may contribute to an increased asthma susceptibility in the offspring. Notably, F-53B exhibits transplacental transfer efficiency comparable to that of PFOS, raising concerns regarding its safety as a PFOS alternative.