title: Environmentally induced epigenetic transgenerational inheritance of ovarian disease.
abstract: 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.
authors.affiliation: School of Biological Sciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Nilsson
authors.forename: Ginger
authors.initials: G
authors.lastname: Larsen
authors.forename: Mohan
authors.initials: M
authors.lastname: Manikkam
authors.forename: Carlos
authors.initials: C
authors.lastname: Guerrero-Bosagna
authors.forename: Marina I
authors.initials: MI
authors.lastname: Savenkova
authors.forename: Michael K
authors.initials: MK
authors.lastname: Skinner
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D004777:Environment; D044127:Epigenesis, Genetic / Q000187:drug effects; D057890:Epigenomics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D040941:Heredity; D008297:Male; D009865:Oocytes / Q000378:metabolism; D010048:Ovarian Cysts / Q000473:pathology; D010049:Ovarian Diseases / Q000235:genetics*; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D000726:Androgen Antagonists; D010080:Oxazoles; C025643:vinclozolin