Perfluorooctanoic acid (PFOA) exposure induces splenic atrophy via overactivation of macrophages in male mice

Perfluorooctanoic acid (PFOA), a synthetic and widely used chemical, has aroused wide public concern due to its persistence, bioaccumulation, and potential toxicity. To investigate splenic atrophy induced by PFOA, male mice were exposed to 0, 0.4, 2, or 10 mg/kg/d PFOA for 28 d. Results demonstrated that spleen weight and relative spleen weight (RSW) decreased in the 2 and 10 mg/kg/d PFOA exposure groups. Iron levels in the spleen and serum were also reduced in all PFOA exposure groups. Weighted gene co-expression network analysis (WGCNA) of 7 043 genes highlighted enrichment in cell cycle, autoimmunity, and anemia in the spleen. In addition, changes in the levels of hemoglobin, platelets, bilirubin, and heme oxygenase-1 were consistent with anemia. The ratio of total macrophages to M1 macrophages in the spleen, phagocytic ability of macrophages, and levels of cytokines such as TNF-α, IL-1β, and IL-6 all increased, thus suggesting the occurrence of autoimmune disorder. Therefore, we concluded that overactivation of macrophages may be an important reason for splenic atrophy induced by PFOA exposure.