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CC BY V4.0, Open Access
Journal article
Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline
PloS one, Vol.9(7), pp.e102091-e102091
2014
Handle:
https://hdl.handle.net/2376/113542
PMCID: PMC4109920
PMID: 25057798
Abstract
Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.
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Details
- Title
- Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline
- Creators
- Mohan Manikkam - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of AmericaM Muksitul Haque - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of AmericaCarlos Guerrero-Bosagna - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of AmericaEric E Nilsson - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of AmericaMichael K Skinner - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America
- Publication Details
- PloS one, Vol.9(7), pp.e102091-e102091
- Academic Unit
- Biological Sciences, School of
- Publisher
- United States
- Grant note
- R01 ES012974 / NIEHS NIH HHS
- Identifiers
- 99900547893901842
- Language
- English
- Resource Type
- Journal article