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Series GSE59510 Query DataSets for GSE59510
Status Public on Jul 17, 2014
Title Environmentally Induced Transgenerational Epigenetic Reprogramming of Primordial Germ Cells and Subsequent Germline [NimbleGen]
Organism Rattus norvegicus
Experiment type Methylation profiling by genome tiling array
Summary A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.
Overall design The F0 generation females were exposed to a vehicle (dimethylsulfoxide DMSO) as control or to vinclozolin, as described in the Methods. The F1 generation offspring were bred to generate the F2 generation and the F2 generation offspring were bred to generate the F3 generation offspring. The timed pregnant F2 generation females were used to isolate the F3 generation control and vinclozolin lineage fetal gonads at the E13 and E16 time points. The F3 generation E13 PGC and E16 prospermatogonia were isolated. DNA was isolated from the freshly isolated cells to examine DNA methylation by methylated DNA immunoprecipitation (MeDIP) followed by analysis on a genome-wide promoter tiling array (Chip) using a comparative hybridization MeDIP-Chip analysis between control and vinclozolin lineage samples as described in Methods. This allowed a comparison of the epigenome alterations in F3 vinclozolin lineage germ cells at E13 and E16. Three separate experimental comparisons of control and vinclozolin-lineage animals involving different germ cell isolations were analyzed with three different MeDIP-Chip analyses at each time point.
Contributor(s) Skinner MK, Gurerrero-Bosagna C, Haque M, Nilsson E, McCarrey J
Citation(s) 23869203
Submission date Jul 17, 2014
Last update date Jul 22, 2014
Contact name Michael K Skinner
Organization name WSU
Department SBS
Street address Abelson 507
City Pullman
State/province WA
ZIP/Postal code 99163
Country USA
Platforms (1)
GPL16994 NimbleGen Rat CpG Island Plus RefSeq Promoter 720k array [100718_RN34_CpG_Refseq_Prom_MeDIP]
Samples (6)
GSM1438556 E16-Vip2/Cip2
GSM1438557 E13-Vip2/Cip1
GSM1438558 E13-Vip1/Cip1
This SubSeries is part of SuperSeries:
GSE59511 Environmentally Induced Transgenerational Epigenetic Reprogramming of Primordial Germ Cells and Subsequent Germline
BioProject PRJNA255513

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
GSE59510_RAW.tar 260.8 Mb (http)(custom) TAR (of GFF, PAIR, TXT)
Raw data provided as supplementary file
Processed data provided as supplementary file

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