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H3K4me3 involvement in long-term effects of sulfomethoxazole on Caenorhabditis elegans over 11 consecutive generations and their first non-exposed progeny

ABSTRACT: Caenorhabditis elegans, a free-living nematode, were exposed to sulfomethaxozale (SMX) for 11 consecutive generations. The F11 nematodes and their first non-exposed progeny (F14’) went through chromatin immune-precipitation at H3K4me3 site and a subsequent DNA-sequencing. Results showed that F11 and F14’ nematodes had 3-fold more H3K4me3 biding genes than the control. These genes showed the highest enrichment in the promoter region with 42.11% and 73.72% in F11 and F14’ nematodes, respectively, indicating increased activity of their regulated genes. In F11 nematodes, the genes regulating metabolic and biosynthetic processes of phospholipid, glycerolipid and glycerophospholipid were significantly activated with a mean enrichment fold change of 50.57. The genes regulating nervous system and development were also activated with a mean enrichment fold change of 65.03 and 58.14, respectively. In F14’ nematodes, 96 and 67 genes showed up- and down-regulations compared with those in F11 nematodes. In the up-regulation, genes regulating development, reproduction and transmembrane transport showed mean enrichment fold changes of 2.52, 22.41 and 34.47, respectively. The down-regulated genes were also related with development, reproduction and transmembrane activities with mean enrichment fold changes ranging from 1.51 to 8.32. Our findings demonstrated the epigenetic involvement in the SMX trans-generational effects.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE90099 | GEO | 2016/11/24

SECONDARY ACCESSION(S): PRJNA354721

REPOSITORIES: GEO

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Project description:In the current study a systematic investigation of life stage, tissue and cell dependent sensitivity to ionizing radiation in the nematode Caenorhabditis elegans was conducted. This revealed that individuals that have reached the post-mitotic L4 stage showed no significant effects with respect to mortality, morbidity or reproduction when subjected to either acute dose ≤6 Gy(1500 mGy/h) or chronic exposure ≤4 Gy( ≤ 100 mGy/h). In contrast, chronic exposure from embryo to young adult stage caused a dose and dose rate dependent reprotoxicitiy with 43% reduction in total brood size at 6.7Gy (107 mGy/h). Systematic targeted irradiation of developmental stages showed that exposure during L1 to young L4 was sufficient to induce reprotoxic effects. Exposure during these stages was associated with a dose rate dependent genotoxic effects on gonads with 1.7 to 3.2 fold increase in germ cell apoptosis in larvae subjected to 40-100 mGy/h, respectively. Importantly, exposure to gamma radiation significantly impaired spermatogenesis in a dose rate dependent manner. The observed reduction in the number of spermatids accounted for xx% of the reprotoxic effects, thus signifying spermatids as the most radiosensitive cell type in C. elegans. Molecular responses analyzed by RNAseq of nematodes irradiated from L1 to L4 stage revealed a significant enrichment of genes related to both male and hermaphrodite reproductive processes. Gene network analysis identified adverse genotoxic effects related to down-regulation of genes required for spindle formation and sperm meiosis/maturation, including smz-1, smz-2 and htas-1. The expression of a subset of 28 set-17 regulated Major Sperm Proteins (MSP) required for spermatids production was correlated to the reduction in reproduction and the number of spermatids, thus corroborating the impairment of spermatogenesis as the major cause of gamma radiation induced life-stage dependent reprotoxic effect. Furthermore, the progeny of irradiated nematodes showed significant embryonal DNA damage that was associated with persistent effect on somatic growth. Unexpectedly, these nematodes did however maintain much of their reproductive capacity in spite of the reduced growth.

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H3K4me3 involvement in long-term effects of sulfomethoxazole on Caenorhabditis elegans over 11 consecutive generations and their first non-exposed progeny

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