DDT exposure echoes through the generations via epigenetic inheritance

Posted by Biome on 24th October 2013 - 0 Comments

The organochlorine insecticide DDT (dichlorodiphenyltrichloroethane) saw worldwide use in the 1940s and 1950s, both to eliminate typhus-carrying insects in Europe and in the World Health Organisation initiative to globally eradicate malaria. The use of DDT as an agricultural insecticide also grew rapidly during this time. However by the 1960s concern over the toxic effects of this insecticide on wildlife, the environment as well as human health, resulted in phasing out of its agricultural use and eventual ban in several countries. However, DDT is currently still used in some countries for disease vector control and agriculture, making concerns over the health hazards relevant today. A recent BMC Medicine study by Michael Skinner from Washington State University, USA, and colleagues, reveals that the detrimental effects of DDT exposure may be carried through the generations via epigenetic inheritance, resulting in the promotion of obesity. Skinner explains more about what the implications of this study, carried out in rats, may be for humans.


What got you interested in the epigenetic effects of environmental toxins?

Over ten years ago we observed the effect that an environmental toxicant exposure during gestation promoted disease not only in the offspring but also in the grand-offspring and great grand-offspring, at the same disease frequency. This did not follow normal genetic rules and appeared to be a form of non-genetic inheritance such as epigenetics. We followed this up and did find the mechanism was epigenetic involving DNA methylation. We defined this phenomenon as environmentally induced epigenetic transgenerational inheritance of disease. This observation is what pushed us into the field of epigenetics.


Are there any other examples, besides DDT, of environmental effects on epigenetic inheritance?

We have found a large number of environmental toxicants, such as fungicides, pesticides, plastic derived compounds and hydrocarbons, which can all promote epigenetic transgenerational inheritance of disease. Other laboratories have also shown abnormal nutrition or stress can promote this phenomenon as well. More recently work by other research groups has shown a growing list of environmental toxicants can promote this.


What kind of impact do you think these findings will have on public health, policy and the clinic?

If your environmental exposure does not only effect you but your great grandchildren, the potential hazards of environmental exposures is significantly increased. This effects policy in requiring we look for transgenerational effects of toxicants, suggests an aspect of disease may in part be what your ancestors were exposed to, and that there may be a major role of epigenetics in disease etiology and evolutionary biology. This can potentially help explain where much of disease that cannot be linked to genetics but is associated with an environmental exposure may come from. Therefore, novel diagnositcs and potential therapeutics for disease can now be considered. The concepts of the research are anticipated to significantly impact clinicians, industry and the public.


What surprised/excited you when you started looking at your data on DDT exposure in rats?

One of the biggest surprises was that over 50 percent of the male and female rats developed obesity and correlated disease. This high frequency was not expected and suggested ancestral exposures such as DDT may be a component of disease susceptibility in our current population. The exciting thing is knowing this may be involved provides novel epigenetic biomarkers/diagnostics and therapy strategies for future clinical use.


What are you up to next?

We are further investigating the molecular aspects of this environmentally induced epigenetic transgenerational inheritance of disease.  However, a major interest is translating these observations to humans.


More about the author(s)

Michael Skinner, Professor at Washington State University, USA.

Michael Skinner is a professor in the School of Biological Sciences at Washington State University, USA, where he obtained his PhD in biochemistry. Skinner underwent his postdoctoral training at the Charles H Best Institute at the University of Toronto, Canada.  During his career he has been on the faculty of the Pharmacology department at Vanderbilt University, USA, and the Reproductive Sciences and Physiology department at the University of California at San Francisco, USA. Skinner also established and was the founding Director of the Washington State University and University of Idaho Center for Reproductive Biology, USA, and the Center for Integrated Biotechnology, USA. His research interests focus on reproductive biology and environmental epigenetics, with studies including insights into the initiation of male sex differentiation, testis development and ovarian primordial follicle development.

Research article

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

Skinner MK, Manikkam M, Tracey R, Guerrero-Bosagna C, Haque M and Nilsson EE
BMC Medicine 2013, 11:228

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