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

Skinner, Michael K.; Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Haque, M. Muksitul; Nilsson, Eric

doi:10.1186/1741-7015-11-228

Cited by 351 publications

(341 citation statements)

References 76 publications

(151 reference statements)

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“…These results are in agreement with previous studies which also found transgenerational increases in susceptibility to ovarian diseases after exposure of F0 generation pregnant rats to vinclozolin [15] or DDT [16]. Experimental exposure of pregnant rats to other environmental toxicants such as jet fuel hydrocarbons, the plastics compounds bisphenol A (BPA) and phthalates, the pesticides permethrin and methoxychlor, and the industrial pollutant dioxin have also been shown to promote a transgenerational increase in ovarian disease [15,42].…”

Section: Discussionsupporting

confidence: 94%

“…In addition, the ovarian granulosa cells from the antral follicles of 6-month-old F3 generation vinclozolin lineage rats showed transgenerational changes in gene expression and alterations in the pattern of DNA methylation compared to F3 generation control lineage rats [15]. Similarly, exposure of F0 generation pregnant rats to the insecticide DDT (dichlorodiphenyltrichloroethane) induced an epigenetic transgenerational increase in ovarian diseases in the F3 generation, which was comprized of primordial follicle loss and increased rates of ovarian cysts [16]. Ancestral exposure to DDT also induced transgenerational changes in F3 generation sperm DNA methylation patterns [16], but epigenetic changes in ovarian somatic cells such as granulosa cell have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, exposure of F0 generation pregnant rats to the insecticide DDT (dichlorodiphenyltrichloroethane) induced an epigenetic transgenerational increase in ovarian diseases in the F3 generation, which was comprized of primordial follicle loss and increased rates of ovarian cysts [16]. Ancestral exposure to DDT also induced transgenerational changes in F3 generation sperm DNA methylation patterns [16], but epigenetic changes in ovarian somatic cells such as granulosa cell have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

et al. 2018

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Two of the most prevalent ovarian diseases affecting women’s fertility and health are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS). Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease. In the current study, transgenerational changes to the transcriptome and epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures. In purified granulosa cells from 20-day-old F3 generation females, 164 differentially methylated regions (DMRs) (P < 1 x 10−6) were found in the F3 generation vinclozolin lineage and 293 DMRs (P < 1 x 10−6) in the DDT lineage, compared to controls. Long noncoding RNAs (lncRNAs) and small noncoding RNAs (sncRNAs) were found to be differentially expressed in both the vinclozolin and DDT lineage granulosa cells. There were 492 sncRNAs (P < 1 x 10−4) in the vinclozolin lineage and 1,085 sncRNAs (P < 1 x 10−4) in the DDT lineage. There were 123 lncRNAs and 51 lncRNAs in the vinclozolin and DDT lineages, respectively (P < 1 x 10−4). Differentially expressed mRNAs were also found in the vinclozolin lineage (174 mRNAs at P < 1 x 10−4) and the DDT lineage (212 mRNAs at P < 1 x 10−4) granulosa cells. Comparisons with known ovarian disease associated genes were made. These transgenerational epigenetic changes appear to contribute to the dysregulation of the ovary and disease susceptibility that can occur in later life. Observations suggest that ancestral exposure to toxicants is a risk factor that must be considered in the molecular etiology of ovarian disease.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

et al. 2018

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“…For example, atrazine inhibits meiosis in mice, but also affects gene expression in ways that can be inherited through the germline in the next generation (Gely-Pernot et al, 2015). Similarly, DDT exposure can result in transgenerational effects (Skinner et al, 2013b, Kabasenche and Skinner, 2014, Song et al, 2014 and at least two fungicides can have transgenerational effects (Skinner, 2011, Skinner et al, 2013a. These observations create an even greater concern.…”

Section: C Transgenerational Effectsmentioning

confidence: 99%

From silent spring to silent night: Agrochemicals and the anthropocene

Hayes

Hansen

2017

Elementa: Science of the Anthropocene

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Hayes, TB and Hansen, M 2017 From silent spring to silent night: Agrochemicals and the anthropocene. Elem Sci Anth, 5: 57, DOI: https://doi.org/10.1525/elementa.246 IntroductionWe are in the Anthropocene and likely experiencing the Earth's sixth mass extinction. The current mass extinction is the first to be caused by a single species, humans. Chemical contaminants in the environment, especially pesticides, are playing an important role in the Anthropocene. Over 85,000 synthetic chemicals exist today (USEPA, 2014, USEPA, 2016b, NIH, 2014. These chemicals represent compounds used in every aspect of life and can end up in the environment (air, water, soil, and biological tissues). Even personal care products and personal use chemicals (such as pharmaceuticals) can persist in the environment ( Yamamoto et al., 2009, D'Abrosca et al., 2008. Although there are many sources and types of chemicals in the environment, pesticides are a significant concern because they are applied directly in the environment in large amounts, particularly by the agricultural industry. Pesticides are defined by the U.S. Environmental Protection Agency as: "any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest; any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant, or any nitrogen stabilizer" (USEPA, 2015c) and include herbicides, fungicides, nematocides, rodenticides, and agents to kill bacteria and viruses. Over the last 75 years, the use of pesticides has increased dramatically and continues to increase. Approximately 2.3 billion kilograms of pesticides are used annually worldwide with the U.S. alone accounting for over 0.45 billion kilograms per year (Alavanja, 2009, USEPA, 2017, USEPA, 2015b. Here, we review evidence that pesticides have altered the gene pool of target organisms and through direct toxic effects and so-called "low dose" effects (effects below concentrations considered safe) have altered landscapes and populations globally REVIEWFrom silent spring to silent night: Agrochemicals and the anthropocene Tyrone B. Hayes * and Martin Hansen *, †We are now living in the Anthropocene, the first time in Earth's history when synthetic chemicalscreated by humans-are damaging the planet and contributing to a major loss of biodiversity. Pesticides are a particular problem in this regard. Agricultural practices changed dramatically following World War II.Methods for the production of nitrogen for manufacturing explosives were adapted for use as fertilizer in agriculture. Further, chemicals used to combat insect vectors for disease during World War II were adapted for the control of insect pests in agriculture. Eventually, herbicides used as defoliants to destroy food supplies and aid in combating soldiers using forests as cover, were customized to control weeds in agriculture. The heavy use of pesticides in agriculture has resulted in global exposure to these chemicals. Travelling through water, air, and in migrating animals, pes...

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“…Michael Skinner, who studies epigenetics at Washington State University in Pullman, has exposed pregnant rats to various environmental contaminants: most recently, the pesticide dichlorodiphenyltrichloroethane (DDT) 16 . Although the chemical had no effect on the weight of the rats' offspring, more than half of the rats' great grandchildren grew fat.…”

Section: Clean Slatementioning

confidence: 99%

Heritability: The family roots of obesity

Willyard¹

2014

Nature

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

Cited by 351 publications

References 76 publications

Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

From silent spring to silent night: Agrochemicals and the anthropocene

Heritability: The family roots of obesity

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