GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE134636 Query DataSets for GSE134636
Status Public on Jul 23, 2019
Title Developmental Dieldrin Exposure Alters DNA Methylation at Genes Related to Dopaminergic Neuron Development and Parkinson’s Disease in Mouse Midbrain
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Human and animal studies have shown that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson’s disease (PD). Despite previous work showing a link between developmental dieldrin exposure and increased neuronal susceptibility to MPTP toxicity in male C57BL/6 mice, the mechanism mediating this effect has not been identified. Here, we tested the hypothesis that developmental exposure to dieldrin increases neuronal susceptibility via genome-wide changes in DNA methylation. Starting at 8 weeks of age and prior to mating, female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin by feeding (every 3 days) throughout breeding, gestation, and lactation. At 12 weeks of age, pups were sacrificed and midbrains were dissected. DNA was isolated and dieldrin-related changes in DNA methylation were assessed via reduced representation bisulfite sequencing (RRBS). We identified significant, sex-specific differentially methylated CpGs (DMCs) and regions (DMRs) by developmental dieldrin exposure (FDR<0.05), including DMCs at the Nr4a2 and Lmx1b genes, which are involved in dopaminergic neuron development and maintenance. Developmental dieldrin exposure had distinct effects on the male and female epigenome. Furthermore, a separate set of changes in DNA methylation was identified after adult exposure to dieldrin, suggesting that adult and developmental dieldrin toxicity may not act through a shared epigenetic mechanism. Together, our data suggest that developmental dieldrin exposure establishes sex-specific poised epigenetic states early in life. These poised epigenomes may mediate sensitivity to additional environmental stimuli and contribute to the development of late-life neurodegenerative disease, including PD.
Overall design RRBS data for developmental exposure: control (n=12; male n=6, female n=6) vs. dieldrin treatment (0.3 mg/kg) (n=12; male n=6, female n=6). RNA-seq data for developmental exposure: control (n=12; male n=6, female n=6) vs. dieldrin treatment (0.3 mg/kg) (n=12; male n=6, female n=6). RRBS data for adult exposure: control (n=5; only male) vs. dieldrin treatment (0.3 mg/kg) (n=5; only male).
Contributor(s) Kochmanski J, VanOeveren SE, Bernstein AI
Citation(s) 30859219
NIH grant(s)
Grant ID Grant title Affiliation Name
R21 ES029205 Dieldrin exposure and synucleinopathy MICHIGAN STATE UNIVERSITY Alison Bernstein
R00 ES024570 Epigenetic effects of adult and developmental exposure to Parkinsonian toxicants MICHIGAN STATE UNIVERSITY Alison Bernstein
Submission date Jul 22, 2019
Last update date Jul 25, 2019
Contact name Alison I Bernstein
Phone 6162340957
Organization name Michigan State University
Department Translational Neuroscience
Lab Bernstein Lab
Street address 400 Monroe Ave NW
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (58)
GSM3960589 P3-E1-052-SN-R
GSM3960590 P3-E1-059-SN-R
GSM3960591 P3-E1-066-SN-R
BioProject PRJNA555989
SRA SRP215922

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
GSE134636_RAW.tar 2.1 Gb (http)(custom) TAR (of COV, H5, TXT)
GSE134636_ToxSci_GEO-Submission_Meta_072219.xls.gz 24.3 Kb (ftp)(http) XLS
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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