Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures

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

doi:10.1371/journal.pone.0031901

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Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures

Journal article

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Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures

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

PloS one, Vol.7(2), pp.e31901-e31901

2012

DOI: https://doi.org/10.1371/journal.pone.0031901

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https://hdl.handle.net/2376/101680

PMCID: PMC3289630

PMID: 22389676

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Abstract

Permethrin - toxicity

Benzhydryl Compounds

Phenols - toxicity

Hydrocarbons - toxicity

Spermatozoa - drug effects

Reproduction - drug effects

Ovarian Follicle - drug effects

Sex Determination Processes - drug effects

DEET - toxicity

Pesticides - toxicity

Epigenesis, Genetic - drug effects

DNA Methylation - drug effects

Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.

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Title: Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures
Creators: Mohan Manikkam - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America
Carlos Guerrero-Bosagna
Rebecca Tracey
Md M Haque
Michael K Skinner
Publication Details: PloS one, Vol.7(2), pp.e31901-e31901
Academic Unit: Biological Sciences, School of
Publisher: Public Library of Science; United States
Grant note: R01 ES012974 / NIEHS NIH HHS ES012974 / NIEHS NIH HHS
Identifiers: 99900546660901842
Language: English
Resource Type: Journal article