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

Mohan Manikkam; Rebecca Tracey; Carlos Guerrero-Bosagna; Michael K Skinner

doi:10.1371/journal.pone.0046249

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

Journal article

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

Mohan Manikkam, Rebecca Tracey, Carlos Guerrero-Bosagna and Michael K Skinner

PloS one, Vol.7(9), pp.e46249-e46249

2012

DOI: https://doi.org/10.1371/journal.pone.0046249

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https://hdl.handle.net/2376/104034

PMCID: PMC3458876

PMID: 23049995

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Abstract

Ovarian Follicle - drug effects

Prostatic Diseases - chemically induced

Polychlorinated Dibenzodioxins - toxicity

DNA Methylation - genetics

Epigenesis, Genetic - drug effects

Spermatozoa - metabolism

Spermatozoa - drug effects

DNA Methylation - drug effects

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.

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Title: Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations
Creators: Mohan Manikkam - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, USA
Rebecca Tracey
Carlos Guerrero-Bosagna
Michael K Skinner
Publication Details: PloS one, Vol.7(9), pp.e46249-e46249
Academic Unit: Biological Sciences, School of
Publisher: Public Library Science; United States
Number of pages: 15
Grant note: NIH, NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) USA Department of Defense (DOD)
Identifiers: 99900546862401842
Language: English
Resource Type: Journal article