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| Status |
Public on Jan 24, 2017 |
| Title |
Mercury-Induced Epigenetic Transgenerational Inheritance of Abnormal Neurobehavior is Correlated with Sperm Epimutations in Zebrafish |
| Organism |
Danio rerio |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant, with human exposures predominantly resulting from fish consumption. Developmental exposure of zebrafish to MeHg is known to alter their neurobehavior. The current study investigated the direct exposure and transgenerational effects of MeHg, at tissue doses similar to those detected in exposed human populations, on sperm epimutations (i.e., differential DNA methylation regions [DMRs]) and neurobehavior (i.e., visual startle and spontaneous locomotion) in zebrafish, an established human health model. F1 generation embryos were exposed to MeHg (0, 1, 3, 10, 30, and 100 nM) for 24 hours ex vivo. F1 generation control and MeHg-exposed lineages were reared to adults and bred to yield the F2 generation, which was subsequently bred to the F3 generation. Direct exposure (F1 generation) and transgenerational actions (F3 generation) were then evaluated. Hyperactivity and visual deficit were observed in the unexposed descendants (F3 generation) of the MeHg-exposed lineage compared to control. An increase in F3 generation sperm epimutations was observed relative to the F1 generation. Investigation of the DMRs in the F3 generation MeHg-exposed lineage sperm revealed associated genes in the neuroactive ligand-receptor interaction and actin-cytoskeleton pathways being effected, which correlate to the observed neurobehavioral phenotypes. Developmental MeHg-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in F3 generation adult zebrafish. Therefore, mercury has the ability to promote the epigenetic transgenerational inheritance of disease in zebrafish, which significantly impacts its environmental health considerations in all species including humans.
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| Overall design |
F1 generation zebrafish embryos were exposed to MeHg. F1 generation control and MeHg-exposed lineages propogated to the F3 generation. Sperm was collected from both F1 and F3 generation fish. The sperm from two fish was combined to create a single pooled sample. Three pools were collected for both control and MeHg treated groups. The methylation characteristics of the pooled samples was estimated using a methylated DNA immunoprecipitation (MeDIP) followed by PE50 sequencing on an Illumina HiSeq 2500 platform.
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| Contributor(s) |
Carvan III MJ, Kalluvila TA, Klingler RH, Larson JK, Pickens M, Mora-Zamorano FX, Connaughton VP, Sadler-Riggleman I, Beck D, Skinner MK |
| Citation missing |
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| Submission date |
Oct 25, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Michael K Skinner |
| E-mail(s) |
skinner@mail.wsu.edu
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| Organization name |
WSU
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| Department |
SBS
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| Street address |
Abelson 507
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| City |
Pullman |
| State/province |
WA |
| ZIP/Postal code |
99163 |
| Country |
USA |
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| Platforms (1) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA350395 |
| SRA |
SRP092038 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE89144_F1.results.csv.gz |
649.0 Mb |
(ftp)(http) |
CSV |
| GSE89144_F3.results.csv.gz |
685.2 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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