Research finds effects of toxins can be inherited

PULLMAN – Blame Grandma’s genes.

New research at Washington State University suggests that environmental toxins can permanently alter the genes of entire generations of animals, causing infertility and disease at levels that don’t decline from one generation to the next.

“The exposure your pregnant grandmother had could induce a disease state in you and you will pass this on to your grandchildren,” according to a summary of the research. “Therefore, the potential hazard of environmental toxins is dramatically increased, in particular for pregnant women in mid-gestation.”

The research, published in the new edition of Science magazine, is the first time that a “transgenerational effect of an environmental toxin” has been demonstrated, said Michael Skinner, director of the Center for Reproductive Biology at WSU.

But it doesn’t show that it has happened – just that it can, he said. Further studies would be needed to show whether the same results are seen at lower, more typical doses of the toxins than were used in Skinner’s study.

“There’s a lot more work to be done to figure it out,” said Jerry Heindel, an expert in reproductive toxicology for one of the National Institutes of Health in Research Triangle Park, N.C. “But it’s very noteworthy in any event. … It will stimulate a lot of good research.”

The study offers one possible way of explaining regional differences in disease and male fertility, Skinner said. And it suggests that toxins may play a role in diseases that previously were thought to be purely genetic.

“It’s a new way to think about disease,” Skinner said in a WSU news release. “We believe this phenomenon will be widespread and be a major factor in understanding how disease develops.”

The study began four years ago under Skinner’s supervision. Gestating female rats whose embryos were at the stage of sex differentiation were exposed to very high levels of vinclozolin, a fungicide, and methoxychlor, a pesticide.

The compounds are known as “endocrine disruptors,” synthetic chemicals that interfere with reproductive hormones.

“They’re present throughout our environment,” Skinner said in a campus presentation Wednesday. “A number of compounds in our environment are basically endocrine disruptors.”

The males of the first generation had lower sperm counts and abnormal sperm production, and about 10 percent were infertile, according to research summaries. The same results appeared at very similar levels in the second, third and fourth generations.

The study – and new research that hasn’t been published – also shows higher rates of disease among the rats whose mothers were exposed to the chemicals, Skinner said.

He notes that the study used very high doses of the compounds – higher than the most-exposed human would ever undergo. The next step is for scientists to study the effects of lower doses on animals, and the presence of the compounds in the environment.

In addition to raising questions about hereditary disease, the research raised the possibility that environmental factors may play a larger role in evolution than previously believed, according to WSU.

Heindel, with the National Institutes of Health, said his federal organization has been interested in finding the “fetal basis of adult disease” in a wide variety of studies.

“What we’ve known for a long time is that the fetus is more sensitive than adults to a lot of environmental toxicants,” he said. That’s especially true during a “window of exposure” when genes are being programmed in embryos – the period when Skinner’s researchers exposed the rats to the pesticides and fungicides.

Various factors can influence development at that stage, in ways that don’t appear until adulthood, Heindel said. “It alters your programming,” he said.

But the fact that WSU scientists found the effects of embryonic exposure to hold steady through succeeding generations is new, he said.