Abstract

Dietary intake is a primary route of exposure to polychlorinated biphenyls (PCBs). The absorption and adverse effects of pollutants are markedly influenced by sex. However, insights into sex-specific differences in PCB oral bioavailability remain limited. In this study, PCB oral bioavailability was assessed in adult female and male Balb/c mice. At different exposure doses, the oral bioavailability of PCBs in female mice (14.2–22.8%) was significantly higher than that in male mice (12.3–18.8%). Correspondingly, males excreted a greater proportion of PCBs via feces, with fecal excretion percentages of 9.50–10.4% in males compared to 6.98–8.13% in females. Mechanistic analyses revealed that the higher PCB oral bioavailability in females was associated with greater dietary lipid assimilation efficiency and elevated postprandial serum apoB-48 levels, which are key indicators of chylomicron-mediated transport of lipophilic pollutants. Gut microbiota analysis revealed a more pronounced increase in Desulfovibrio abundance in female mice (from 6.57% to 18.18%) than in males (4.95% to 7.89%). This sex-specific change may be related to the impaired intestinal barrier and thereby enhanced PCB absorption in female mice. Liver transcriptomics revealed that PCB exposure primarily altered lipid metabolism-related genes in female mice, while male mice exhibited stronger responses in xenobiotic metabolism and DNA toxicity pathways. This study advances our understanding of the mechanisms driving sex differences in PCB oral bioavailability and hence the adverse effects, offering key insights for crafting targeted strategies to reduce PCB exposure across diverse subpopulations.