Multi-generational obesogenic effects of sulfomethoxazole on Caenorhabditis elegans through epigenetic regulation

Increasing concerns are earned on the multigenerational hazards of antibiotics due to the connection between their mother-children transfer via cord blood and breast milk and obesity in the children. Currently, Caenorhabditis elegans was exposed to sulfamethoxazole (SMX) over 11 generations (F0-F10). Indicators of obesogenic effects and gene expressions were measured in each generation and also in T11 to T13 that were the offspring of F10. Biochemical analysis results showed that SMX stimulated fatty acids in most generations including T13. The stimulation was resulted from the balance between enzymes for fatty acid synthesis (e.g., fatty acid synthetase) and those for its consumption (e.g., fatty acid transport protein). Gene expression analysis demonstrated that the obesogenic effects of SMX involved peroxisome proliferator activated receptors (PPARs, e.g., nhr-49) and insulin/insulin-like signaling (IIS) pathways (e.g., ins-1, daf-2 and daf-16). Further epigenetic analysis demonstrated that SMX caused 3-fold more H3K4me3 binding genes than the control in F10 and T13. In F10, the most significantly activated genes were in metabolic and biosynthetic processes of various lipids, nervous system and development. The different gene expressions in T13 from those in F10 involved development, growth, reproduction and responses to chemicals in addition to metabolic processes.