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Series GSE59555 Query DataSets for GSE59555
Status Public on Jul 22, 2014
Title Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations
Organism Rattus norvegicus
Experiment type Methylation profiling by genome tiling array
Summary Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.
 
Overall design Methylated sperm DNA was isolated from rats ancestrally exposed to plastics (Bip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Bip1/Cip1, Bip2/Cip2, and Bip3/Cip3), resulting in three arrays for the treatment.
 
Contributor(s) Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK
Citation(s) 23359474
Submission date Jul 18, 2014
Last update date Jul 22, 2014
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 (3)
GSM1386860 Bip2/Cip2
GSM1386866 Bip1/Cip1
GSM1386871 Bip3/Cip3
Relations
BioProject PRJNA255883

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
GSE59555_BipRegionsCombined.csv.gz 191.9 Kb (ftp)(http) CSV
GSE59555_RAW.tar 156.2 Mb (http)(custom) TAR (of GFF, PAIR)
Raw data provided as supplementary file
Processed data are available on Series record

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