Abstract

Perfluorooctanoic acid (PFOA) in soil poses a significant threat to reptile health. Given the global decline in reptile abundance and diversity, understanding reptile responses to prolonged PFOA-contaminated soil is urgently needed. In this study, Eremias argus , small lizards distributed across northern China, were exposed to PFOA (0.05 and 0.5 mg/kg) for 60 days. PFOA burden, physiological parameters, histopathological features, untargeted metabolomics, and 16S rDNA sequencing were performed to investigate the effects of soil PFOA exposure. The results revealed pronounced sex-dependent differences in PFOA accumulation and associated biological responses. Males exhibited significantly higher internal PFOA levels, whereas females showed comparatively lower burdens, which may be associated with maternal transfer of PFOA to eggs. These sex-dependent differences were accompanied by distinct pathological and metabolic alterations. Specifically, males exhibited severe intestinal barrier damage, reduced abundance of Bacteroidetes , and metabolic disturbances related to bile acid homeostasis. In contrast, females maintained relatively intact intestinal architecture and more stable Bacteroidetes populations, together with comparatively stable bile acid–related metabolic profiles, which potentially facilitating contaminant excretion. Overall, these findings provide mechanistic insights into how soil PFOA exposure may affect reptile physiology during sensitive life-history stages, thereby offering relevant information for future ecological risk assessments.