Endosulfan isomers and sulfate metabolite induced reproductive toxicity in Caenorhabditis elegans involves genotoxic...

Endosulfan is enlisted as one of the persistent organic pollutants (POPs) and exists in the form of its α and β isomers in the environment as well as in the form of endosulfan sulfate, a toxic metabolite. General endosulfan toxicity has been investigated in various organisms, but the effect of the isomers and sulfate metabolites on reproductive function is unclear. This study was aimed at studying the reproductive dysfunction induced by endosulfan isomers and its sulfate metabolite in Caenorhabditis elegans (C. elegans). We also determined a role for the DNA-damage-checkpoint gene hus-1. Compared to β-endosulfan and its sulfate metabolite, α-endosulfan caused a dramatically higher level of germ cell apoptosis, which was regulated by DNA damage signal pathway. Both endosulfan isomers and the sulfate metabolite induced germ cell cycle arrest. Loss-of-function studies using hus-1, egl-1, and cep-1 mutants revealed that hus-1 specifically influenced the fecundity, hatchability, and sexual ratio after endosulfan exposure. Our data provide clear evidence that the DNA-checkpoint gene hus-1 has an essential role in endosulfan-induced reproductive dysfunction and that α-endosulfan exhibited the highest reproductive toxicity among the different forms of endosulfan.