Reproductive Influences of Erythromycin and Sulfamethoxazole on Caenorhabditis elegans over Generations Mediated by Lipid Metabolism

Antibiotics are emerging pollutants with pseudo-persistence. However, their reproductive toxicities over generations and underlying mechanisms were seldom explored. In the present study, reproductive effects of erythromycin(ERY) and sulfamethoxazole(SMZ) were studied on Caenorhabditis elegans (C. elegans) with multi-generational exposure from F1 to F4, and their effects in the non-direct exposed offspring of F1 and F4(T4 and T4’) were explored to investigate trans-generational outcomes. At high concentrations, ERY and SMZ inhibited the reproduction and the inhibition decreased with more generations’ exposure. At low concentrations, SMZ stimulated reproduction in T4, opposite to its inhibition in F1. Further analysis on ten enzymes and proteins in lipid and glucolipid metabolism showed that ERY commonly inhibited fatty acid synthetase(FAS) in F1 to F4, while ERY and SMZ showed stimulation and inhibition on other biochemicals. Integrated biomarker response(IBR) index values showed that ERY and SMZ stimulated the overall metabolism in F1, and the stimulation decreased and even altered to inhibition in later generations. When comparing multi- and trans-generational effects, ERY and SMZ at high concentration caused inhibition on reproduction in T4 and stimulation in T4’, which were opposite to those in F1 and F4.