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Series GSE59109 Query DataSets for GSE59109
Status Public on Jul 07, 2014
Title Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility [NimbleGen]
Organism Rattus norvegicus
Experiment type Methylation profiling by genome tiling array
Summary Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that correlates with adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.
Overall design The isolated Sertoli cell populations from three different groups of animals that were ancestrally exposed to vinclozolin during days 8-14 (E8-14) of fetal development and cell isolates were used to obtain Sertoli cell RNA and DNA from F3 generation control and vinclozolin lineages. The control and vinclozolin lineage Sertoli cell DNA was used in a methylated DNA immunoprecipitation (MeDIP) and genome wide promoter tiling array (Chip) analysis (MeDIP-Chip). Three different comparative (amplified MeDIP vs. amplified MeDIP) hybridizations experiments included in three sub-arrays were performed by Nimblegen. Each comparative hybridization experiment contained one biological replicate of Sertoli cell Whole Genome Amplified-MeDIP-DNA sample from each lineage-treatment.
Contributor(s) Guerrero-Bosagna C, Savenkova M, Haque MM, Nilsson E, Skinner MK
Citation(s) 23555832
Submission date Jul 06, 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)
GPL18610 NimbleGen Rat CpG Island Plus RefSeq Promoter 720k array [090618_RN34_CpG_Refseq_Prom_MeDIP]
Samples (3)
GSM1428772 Vin1_SC6/ Con1_SC2
GSM1428773 Vin2_SC7/ Con2_SC8
GSM1428774 Vin3_SC3/ Con3_SC4
This SubSeries is part of SuperSeries:
GSE59110 Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility
BioProject PRJNA254430

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

Supplementary file Size Download File type/resource
GSE59109_RAW.tar 156.8 Mb (http)(custom) TAR (of CSV, GFF, PAIR)
Raw data provided as supplementary file
Processed data provided as supplementary file

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