PMID- 25612189 OWN - NLM STAT- MEDLINE DCOM- 20151019 LR - 20181202 IS - 1520-5851 (Electronic) IS - 0013-936X (Linking) VI - 49 IP - 4 DP - 2015 Feb 17 TI - Endosulfan isomers and sulfate metabolite induced reproductive toxicity in Caenorhabditis elegans involves genotoxic response genes. PG - 2460-8 LID - 10.1021/es504837z [doi] AB - Endosulfan is enlisted as one of the persistent organic pollutants (POPs) and exists in the form of its alpha and beta 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 beta-endosulfan and its sulfate metabolite, alpha-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 alpha-endosulfan exhibited the highest reproductive toxicity among the different forms of endosulfan. FAU - Du, Hua AU - Du H AD - Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, CAS and Anhui Province , Hefei, Anhui, PR China. FAU - Wang, Min AU - Wang M FAU - Dai, Hui AU - Dai H FAU - Hong, Wei AU - Hong W FAU - Wang, Mudi AU - Wang M FAU - Wang, Jingjing AU - Wang J FAU - Weng, Nanyan AU - Weng N FAU - Nie, Yaguang AU - Nie Y FAU - Xu, An AU - Xu A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150204 PL - United States TA - Environ Sci Technol JT - Environmental science & technology JID - 0213155 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Calcium-Binding Proteins) RN - 0 (Ced-4 protein, C elegans) RN - 0 (Ced-9 protein, C elegans) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 8QTV9M19B2 (endosulfan sulfate) RN - EC 3.4.22.- (Caspases) RN - EC 3.4.22.- (ced-3 protein, C elegans) RN - OKA6A6ZD4K (Endosulfan) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Caenorhabditis elegans/*drug effects/genetics/*physiology MH - Caenorhabditis elegans Proteins/genetics/metabolism MH - Calcium-Binding Proteins/genetics MH - Caspases/genetics MH - DNA Damage/drug effects MH - Dose-Response Relationship, Drug MH - Endosulfan/*analogs & derivatives/chemistry/metabolism/*toxicity MH - Female MH - Gene Expression Regulation/drug effects MH - Isomerism MH - Longevity/drug effects MH - Male MH - Mutation MH - Proto-Oncogene Proteins c-bcl-2/genetics MH - Reproduction/drug effects/*genetics MH - Sex Ratio MH - Signal Transduction/drug effects MH - Toxicity Tests/methods EDAT- 2015/01/23 06:00 MHDA- 2015/10/20 06:00 CRDT- 2015/01/23 06:00 PHST- 2015/01/23 06:00 [entrez] PHST- 2015/01/23 06:00 [pubmed] PHST- 2015/10/20 06:00 [medline] AID - 10.1021/es504837z [doi] PST - ppublish SO - Environ Sci Technol. 2015 Feb 17;49(4):2460-8. doi: 10.1021/es504837z. Epub 2015 Feb 4.