Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity

BMC Medicine

Eric E Nilsson¹  Muksitul Haque¹  Carlos Guerrero-Bosagna¹  Rebecca Tracey¹  Mohan Manikkam¹  Michael K Skinner¹ 

[1] Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA

关键词: Maternal transmission;    Disease etiology;    Epimutations;    Obesity associated disease;    Metabolic syndrome;    Environmental epigenetics;   

Others  :  855633
DOI  :  10.1186/1741-7015-11-228

 received in 2013-05-15, accepted in 2013-09-27,  发布年份 2013

【 摘 要 】

Background

Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease.

Methods

Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm.

Results

The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity.

Conclusions

Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance.

【 授权许可】

   
2013 Skinner et al.; licensee BioMed Central Ltd.

【 图 表 】

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