Environmentally induced epigenetic transgenerational inheritance of ovarian disease

Eric Nilsson; Ginger Larsen; Mohan Manikkam; Carlos Guerrero-Bosagna; Marina I Savenkova; Michael K Skinner

doi:10.1371/journal.pone.0036129

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Environmentally induced epigenetic transgenerational inheritance of ovarian disease

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Environmentally induced epigenetic transgenerational inheritance of ovarian disease

Eric Nilsson, Ginger Larsen, Mohan Manikkam, Carlos Guerrero-Bosagna, Marina I Savenkova and Michael K Skinner

PloS one, Vol.7(5), pp.e36129-e36129

2012

DOI: https://doi.org/10.1371/journal.pone.0036129

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https://hdl.handle.net/2376/108387

PMCID: PMC3343040

PMID: 22570695

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Abstract

Transcriptome

Gene Expression Profiling

Gene Regulatory Networks

Gene-Environment Interaction

Granulosa Cells - drug effects

Granulosa Cells - metabolism

Ovarian Cysts - pathology

Epigenesis, Genetic - drug effects

Ovarian Follicle - metabolism

Ovarian Diseases - genetics

Epigenomics

Oocytes - metabolism

Androgen Antagonists - pharmacology

Heredity

Rats, Sprague-Dawley

Gene Expression Regulation - drug effects

Oxazoles - pharmacology

Ovarian Follicle - pathology

DNA Methylation - drug effects

Signal Transduction

The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

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Title: Environmentally induced epigenetic transgenerational inheritance of ovarian disease
Creators: Eric Nilsson - School of Biological Sciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA
Ginger Larsen
Mohan Manikkam
Carlos Guerrero-Bosagna
Marina I Savenkova
Michael K Skinner
Publication Details: PloS one, Vol.7(5), pp.e36129-e36129
Academic Unit: Biological Sciences, School of
Publisher: Public Library Science; United States
Number of pages: 18
Grant note: National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) Department of Defense; United States Department of Defense National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Identifiers: 99900547041301842
Language: English
Resource Type: Journal article