Dataset Information


Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility [NimbleGen]

ABSTRACT: 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. 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.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Marina Savenkova   Carlos Guerrero-Bosagna  Eric Nilsson  Md M Haque  Michael K Skinner 

PROVIDER: E-GEOD-59109 | ArrayExpress | 2014-07-07



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