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| Status |
Public on Nov 19, 2020 |
| Title |
Epigenome-Wide Association Study for Atrazine Induced Transgenerational Histone Retention Sperm Epigenetic Biomarkers for Disease |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Atrazine is a common agricultural herbicide previously shown to promote epigenetic transgenerational inheritance of disease to subsequent generations. The current study was designed as an epigenome-wide association study (EWAS) to identify transgenerational sperm disease associated differential histone retention regions (DHRs). Gestating female F0 generation rats were transiently exposed to atrazine during the period of embryonic gonadal sex determination, and then subsequent F1, F2, and F3 generations obtained in the absence of any continued exposure. The transgenerational F3 generation males were assessed for disease and sperm collected for epigenetic analysis. Pathology was observed in late pubertal onset and for testis disease, prostate disease, kidney disease, lean pathology, and multiple disease. For these pathologies, sufficient numbers of individual males with only a single specific disease were identified. The sperm DNA and chromatin were isolated from adult one-year animals with the specific diseases and analyzed for DHRs with histone chromatin immunoprecipitation (ChIP) sequencing. Transgenerational F3 generation males with or without disease were compared to identify the disease specific epimutation biomarkers. No common DHRs were found among all the pathologies. Epimutation gene associations were identified and found to correlate to previously known disease linked genes.
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| Overall design |
Analysis of the transgenerational actions of atrazine used outbred Sprague Dawley female rats (F0 generation) transiently exposed (25 mg/kg body weight atrazine daily) during days 8 to 14 of gestation. The F1 generation animals (direct fetal exposure) were bred to generate the F2 generation (direct germline exposure), which were bred to generate the F3 generation (transgenerational so no direct exposure). A control lineage used F0 generation gestating females administered vehicle control dimethyl sulfoxide (DMSO). The control and atrazine lineages were aged to 1 year and euthanized for pathology and sperm epigenetic analysis. No sibling or cousin breedings (crosses) were used to avoid any inbreeding artifacts in either the control or atrazine lineages. Generally 6–8 founder gestating females from different litters were bred and 25–50 individuals of each sex obtained for each generation.
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| Web link |
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239380
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| Contributor(s) |
Thorson JL, Beck D, Maamar MB, Nilsson E, Margaux M, Skinner MK |
| Citation(s) |
33326428 |
| |
| Submission date |
Aug 20, 2020 |
| Last update date |
Feb 18, 2021 |
| Contact name |
Michael K Skinner |
| E-mail(s) |
[email protected]
|
| Organization name |
WSU
|
| Department |
SBS
|
| Street address |
Abelson 507
|
| City |
Pullman |
| State/province |
WA |
| ZIP/Postal code |
99163 |
| Country |
USA |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (67)
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| Relations |
| BioProject |
PRJNA658259 |
| SRA |
SRP278178 |
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