title: Endosulfan isomers and sulfate metabolite induced reproductive toxicity in Caenorhabditis elegans involves genotoxic response genes.
abstract: 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.
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, CAS and Anhui Province , Hefei, Anhui, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Du
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.forename: Mudi
authors.initials: M
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.forename: Nanyan
authors.initials: N
authors.lastname: Weng
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Nie
authors.forename: An
authors.initials: A
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D020169:Caspases / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004726:Endosulfan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007536:Isomerism; D008136:Longevity / Q000187:drug effects; D008297:Male; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012098:Reproduction / Q000187:drug effects / Q000235:genetics*; D012744:Sex Ratio; D015398:Signal Transduction / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C087233:Ced-9 protein, C elegans; D019253:Proto-Oncogene Proteins c-bcl-2; C544689:endosulfan sulfate; D020169:Caspases; C089223:ced-3 protein, C elegans; D004726:Endosulfan