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E-GEOD-59277 - Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease [NimbleGen]

Status
Released on 17 July 2014, last updated on 18 July 2014
Organism
Rattus norvegicus
Samples (6)
Array (1)
Protocols (7)
Description
The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. Granulosa cells from large antral follicles were collected and evaluated from F3 generation rats that were ancestrally exposed to one of the five different treatments: Vinclozolin, Pesticide (includes permethrin and DEET), Plastics (includes BPA, DBP and DEHP), Low-dose Plastics (50% of Plastics dose), Dioxin, Hydrocarbon (Jet fuel JP8), or DMSO vehicle as Control. Vinclozolin lineage alterations in differentially DNA methylated regions (DMR) in the granulosa cells was investigated by using a methylated DNA immunoprecipitation (MeDIP) procedure followed by comparative hybridization on a genome wide promoter tiling array (Chip), termed an MeDIP-Chip assay. The DNA fractions from four animals of the same treatment group were pooled to create three different pooled DNA samples from each of the two treatment groups (experimental vs. control). These DNA samples were then used for methylated DNA immunoprecipitation (MeDIP) using Nimblegen microarrays. Each MeDIP sample was then used to preform three different comparative (amplified MeDIP vs. amplified MeDIP) hybridization experiments (3 sub-arrays), each encompassing DNA samples from 24 animls (3 treatment and 3 control groups).
Experiment type
methylation profiling by array 
Contacts
Michael K Skinner <skinner@mail.wsu.edu>, Carlos Guerrero-Bosagna, Eric Nilsson, G Larson, M Manikkam, Marina Savenkova
Citation
Environmentally induced epigenetic transgenerational inheritance of ovarian disease. Nilsson E, Larsen G, Manikkam M, Guerrero-Bosagna C, Savenkova MI, Skinner MK. , PMID:22570695
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-59277.idf.txt
Sample and data relationshipE-GEOD-59277.sdrf.txt
Raw data (2)E-GEOD-59277.raw.1.zip, E-GEOD-59277.raw.2.zip
Additional data (1)E-GEOD-59277.additional.1.zip
Array designA-GEOD-18610.adf.txt
Links