Transcriptomics

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Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations


ABSTRACT: Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. Methylated sperm DNA was isolated from rats ancestrally exposed to dioxin (Hip). 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 (Hip1/Cip1, Hip2/Cip2, and Hip3/Cip3), resulting in three arrays for the treatment.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Mohan Manikkam   Rebecca Tracey  Carlos Guerrero-Bosagna  Michael K Skinner 

PROVIDER: E-GEOD-59552 | ArrayExpress | 2014-07-22

SECONDARY ACCESSION(S): GSE59552PRJNA255886

REPOSITORIES: GEO, ArrayExpress

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Publications

Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

Manikkam Mohan M   Tracey Rebecca R   Guerrero-Bosagna Carlos C   Skinner Michael K MK  

PloS one 20120926 9


Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease wa  ...[more]

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