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Chemical mixtures may prompt transgenerational obesity

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Two new related studies, both conducted by Michael Skinner and colleagues at Washington State University, indicate that prenatal exposure to chemical mixtures can produce obesity and adverse reproductive health effects in multiple generations. What is noteworthy about the results is that while the first generation examined was exposed prenatally, the third generation was never directly exposed, indicating that the effects are occurring through epigenetic changes. While previous studies by Dr Skinner and colleagues have examined transgenerational effects of chemical exposures (CW 3 October 2012), these are the first in which they investigated adult obesity as a health outcome of such exposures.

In one study, rats were exposed to a mixture of bisphenol A (BPA) and two phthalates, dibutyl phthalate (DBP) and bis(2-ethylhexyl)phthalate (DEHP), compounds widely used in various plastics. For the other, rats were exposed to a jet fuel mixture called JP8. The compounds for both studies were chosen because their widespread use makes potential exposure effects relevant to human health, explained Dr Skinner. BPA, DBP and DEHP are used in many consumer products. In certain locations, the jet fuel is used to control road dust. The compounds' health effects are also of interest to the US Department of Defense, a funder of the research.

In the plastics study, rats exposed prenatally developed obesity, ovarian and testis disease, and pubertal abnormalities, as did the third generation never directly exposed. Rats exposed prenatally to the mixture also developed kidney and prostate disease. Similarly, in the jet fuel study, rats exposed prenatally had an increased incidence of obesity and ovarian disease, as did the third generation. Rats exposed prenatally to jet fuel also had an increased incidence of kidney abnormalities, and in the males, prostate and pubertal abnormalities.

In both studies, the researchers identified DNA methylation regions associated with the epigenetic changes responsible for the observed transgenerational effects. Results of both studies, the researchers say, indicate that these chemical mixtures can prompt epigenetic changes for which sperm DNA methylation regions can act as potential biomarkers for what they call “ancestral environmental exposures”. These findings will also contribute to the growing body of literature describing the environmental and epigenetic origins of adult onset disease, said Dr Skinner.

The plastics study is published in PlosOne and the jet fuel study in the Journal of Reproductive Toxicology.

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