Pregnant rats exposed to an industrial pollutant passed on a variety of diseases to their unexposed great-grandkids, according to a study published Wednesday.
Washington State University scientists found that third-generation offspring of pregnant rats exposed to dioxin had high rates of kidney and ovarian diseases as well as early onset of puberty. They also found changes in the great-grandsons' sperm.
The great-grandkids – the first generation not directly exposed to dioxin – inherited their health conditions through cellular changes controlling how their genes were turned on and off, the researchers reported.
The findings add to a body of research suggesting that the health consequences of exposure to environmental chemicals might be passed to future generations.
“Not only does the individual exposed get the disease, but it’s transmitted to great-grandchildren with no exposure,” said Michael Skinner of Washington State University, who is the senior author of the study, which was published in the journal PLoS One. Skinner is a pioneer in epigenetics – the study of inherited changes in gene expression.
Dioxins, which have been linked to cancer, reproductive disorders and other health problems, are industrial byproducts created by waste incinerators and other processes.
The dioxin doses used in the study were low for lab rats, but are higher than most people’s exposures from the environment. The study raises questions that won’t be easy to answer about people exposed to dioxins from food and industrial sources.
“The study is a nice demonstration of the large scope of damage from a low-dose dioxin,” said Jennifer Wolstenholme, a biochemist who specializes in epigenetics at the University of Virginia. She was not involved with the research.
One of the most interesting findings, she said, was that multiple organ systems were affected in the rats.
Dioxins have declined in food and the environment over the past few decades because emissions from many industries, including pulp and paper mills, smelters and waste incinerators, have been regulated.
The new study focused on a specific dioxin, known as TCDD, a component of the herbicide Agent Orange that was used during the Vietnam War.
Among Vietnamese people exposed to Agent Orange, a high rate of cancers has been found, and their children have had many birth defects and other health problems, too. Vietnam veterans from the United States also were highly exposed, and the U.S. government has determined that certain cancers and other disorders are “presumptive diseases” in veterans who handled Agent Orange.
The new study examined how dioxin exposure affects a person’s epigenome – a road map of chemical changes to DNA and associated proteins. As a fetus develops, its epigenome is reprogrammed, and it can be permanently altered by exposures. The epigenome is then passed down through generations – along with susceptibility to adult-onset disease.
“The cause of the higher rates of disease in these [third generation] animals was not due to direct exposure, but rather through transmission of changes in the code that regulates gene expression,” said Abby Benninghoff, who specializes in epigenetics at Utah State University. She was not involved with the study.
Scientists have long known that environmental exposures can cause genetic mutations. But now epigenetics experts are finding that some exposures seem capable of changing how genes are expressed, or turned on and off, without actually damaging the genes. These changes then can be inherited by future generations.
The findings are not directly applicable to humans, researchers said. The way the animals were dosed is not the same way people are exposed to dioxins, and the moms were dosed for a few days – roughly similar to the first trimester – which does not mimic typical human exposure that is low and gradual but builds over time, Wolstenholme said. Humans and rats also clear dioxin from their bodies differently, she said.