Damage from toxins can pass to offspring

Scientists have shown for the first time that exposure to environmental toxins can cause permanent genetic changes that are passed down through generations.

The research on rats by a team of scientists led by Michael Skinner at Washington State University in Pullman, Wash., may hold the key to the mystery of male infertility, which some researchers say has been increasing for unknown reasons for 20 years.

According to a report in today’s edition of the journal Science, Skinner’s team was working with two commonly used chemicals, an insecticide called methoxychlor and a fungicide called vinclozolin. Both are known to cause infertility in the male offspring of pregnant animals.

The scientists were looking at the rats and their offspring. But when the offspring had offspring, the researchers were shocked by what they found in this second generation. And they were even more surprised by subsequent generations of the lab rats.

“Lo and behold they had the same” infertility problems, says Skinner, director of the university’s Center for Reproductive Biology.

Not only the grandsons but also the great-grandsons and great-great grandsons of the exposed mother were similarly affected. The scientists had discovered a mechanism that permanently changed the reproductive cells.

“That (the changes are) carried down through the generations is what’s new and novel here,” says Paul Turek, a male infertility specialist at the University of California at San Francisco. “Everyone agrees that exposure of the fetus at a certain critical time can cause malformed organs and birth defects. But no one ever imagined this might persist at some level for three more generations.”

Skinner notes that rat studies cannot necessarily be applied to humans, but he said the findings warrant a close look at the potential health hazards of environmental chemicals.

The exposure appears to produce what’s called an epigenetic effect, in which a chemical modification of the DNA in the animal’s reproductive cells causes an alteration with potentially disastrous results — in this case, infertility.

Epigenetic effects are generally erased with each new generation when the cells that form the sperm or eggs are created in the embryo. But in this case, the affected genes maintained the alteration and escaped the reprogramming process.

Skinner cautions that the doses used in his research are higher than those normally found in the environment. He plans to begin testing at lower doses to see whether the same changes appear.

Human exposure to methoxychlor, which is being phased out in the USA, and vinclozolin is mostly restricted to agricultural workers, though there’s not much data to go on, Skinner says. He expects that other researchers will now begin looking for similar effects in people.

But “to the extent that it’s been studied, the epigenetic effects seen in rodents are similar to those seen in humans,” says John McCarrey, an expert on epigenetics at the University of Texas at San Antonio.

The findings may one day facilitate new diagnostic approaches and therapies, Skinner says. For example, doctors would be on the lookout much earlier for certain diseases if they knew that their patients’ ancestors had been exposed to certain toxins, he says.