NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE57693 Query DataSets for GSE57693
Status Public on May 16, 2014
Title Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures.
Organism Rattus norvegicus
Experiment type Methylation profiling by genome tiling array
Summary Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.
Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.
 
Overall design Methylated sperm DNA was isolated from rats ancestrally exposed to plastics (Bip), vinclozolin (Vip), pesticides (Pip), dioxin (Hip), jet fuel (Jip) or control vehicle (Cip). Three independent samples from each treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. For each treatment, treated samples were paired with control samples and hybridized together on arrays (Bip1/Cip1, Bip2/Cip2, Bip3/Cip3, Vip1/Cip1, etc.), resulting in three arrays per treatment group.
 
Contributor(s) Manikkam M, Gurerrero-Bosagna C, Tracey R, Haque M, Skinner MK
Citation(s) 22389676, 24937757
Submission date May 15, 2014
Last update date Jul 29, 2019
Contact name Michael K Skinner
E-mail(s) skinner@mail.wsu.edu
Organization name WSU
Department SBS
Street address Abelson 507
City Pullman
State/province WA
ZIP/Postal code 99163
Country USA
 
Platforms (1)
GPL18610 NimbleGen Rat CpG Island Plus RefSeq Promoter 720k array [090618_RN34_CpG_Refseq_Prom_MeDIP]
Samples (15)
GSM1386860 Bip2/Cip2
GSM1386861 Vip3/Cip3
GSM1386862 Pip3/Cip3
Relations
BioProject PRJNA247732

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE57693_BipRegionsCombined.csv.gz 191.9 Kb (ftp)(http) CSV
GSE57693_HipRegionsCombined.csv.gz 152.8 Kb (ftp)(http) CSV
GSE57693_JipRegionsCombined.csv.gz 109.6 Kb (ftp)(http) CSV
GSE57693_PipRegionsCombined.csv.gz 230.7 Kb (ftp)(http) CSV
GSE57693_RAW.tar 540.9 Mb (http)(custom) TAR (of GFF, PAIR)
GSE57693_VipRegionsCombined.csv.gz 86.3 Kb (ftp)(http) CSV
Processed data are available on Series record
Raw data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap