Contact: 509/335-4846, cwinner@wsu.edu
WSU Study Shows Environmental Toxins Can Cause Inherited Diseases
PULLMAN, Wash. -- A disease you are suffering today could be a
result of your great-grandmother being exposed to an environmental
toxin during pregnancy - and you may already have passed it along
to your children.
That's the conclusion reached by researchers at Washington State
University, who have found that exposure to an environmental toxin
during embryonic development can cause an animal, and almost all of
its descendents, to develop adult-onset illnesses such as cancer
and kidney disease. Their discovery suggests that toxins may have
played a role in the rapid increase in localized geographic areas
of diseases that were previously thought to be caused primarily by
genetic mutations.
"It's a new way to think about disease," said Michael K. Skinner,
director of the Center for Reproductive Biology. "If this pans out,
it gives us a host of new diagnostic and therapeutic tools." He
said it also underscores the potential long-term hazards of
environmental contaminants.
The work is reported in two papers in the September 14 issue of the
journal Endocrinology. It builds on the group's 2005 finding that
exposure to a toxin during embryonic development can cause
fertility problems in male rats that are passed to later
generations.
In the current study, Skinner and a team of WSU researchers
exposed pregnant rats to an environmental toxin during the period
that the sex of their offspring was being determined. At that stage
of development, the genes of the male embryo's sex cells (future
sperm) are uniquely vulnerable to reprogramming.
The researchers used vinclozolin, a fungicide commonly used in
vineyards. Vinclozolin belongs to the class of compounds called
endocrine disruptors, synthetic chemicals that interfere with the
normal functioning of reproductive hormones. Skinner's group used
higher levels of the toxin than are normally present in the
environment, but their study raises concerns about the long-term
impacts of such toxins on human and animal health, particularly in
exposures during early- to mid-pregnancy (6 weeks to 5 months in
humans). Further work will be needed to determine whether lower
levels have similar effects.
Pregnant rats that were exposed to vinclozolin produced male
offspring with low sperm counts and a high incidence of adult-onset
diseases. Despite their low fertility, those males were still able
to produce offspring. When they were mated with females that had
not been exposed to the toxins, their offspring had the same
problems. The effect persisted through four generations, with about
85 percent of the offspring in each generation developing
conditions such as breast tumors, prostate disease, kidney disease,
immune system abnormalities, and premature aging. Some mice came
down with just one disease, but the majority suffered multiple
ailments.
"Only the original generation mother was exposed to the
environmental toxicant," said Skinner. "A human analogy would be if
your grandmother was exposed to an environmental toxicant during
mid-gestation, you may develop a disease state even though you
never had direct exposure, and you may pass it on to your
great-grandchildren."
The study shows the potential impact of so-called epigenetic
inheritance, which refers to the transmission from parent to
offspring of biological information that is not encoded in the DNA
sequence. Instead, the information stems from small chemicals, such
as methyl groups, that become attached to the DNA. In epigenetic
transmission, the DNA sequences - the genes - remain the same, but
the chemical modifications change the way the genes work and when
they "turn on" and "turn off."
The team identified 25 segments of DNA in the affected rats that
had altered patterns of methyl groups compared to control rats.
Their results suggest the genes controlling susceptibility to the
observed diseases lie somewhere within those 25 segments. Skinner
said the broad-spectrum effect of the changes, causing diseases in
many organ systems, was a notable result that could provide
valuable clues about how diseases develop.
According to Skinner, such changes might play a role in human
diseases such as breast cancer and prostate disease, whose
frequency is increasing faster than would be expected if they were
the result of genetic mutations alone. Scientists have long known
about epigenetic changes, but their high rate of heritability and
their importance in the control of gene activity were not
appreciated until recently.
Skinner said the finding that an environmental toxin can
permanently reprogram a heritable trait also may alter our concept
of evolutionary biology. Traditional evolutionary theory maintains
that the environment is primarily a backdrop on which selection
takes place, and that differences between individuals arise from
random mutations in the DNA. The work by Skinner and his group
raises the possibility that environmental factors may play a much
larger role in evolution than has been realized before.
This research was supported by a grant to Skinner from the National
Institutes of Health.
Related Web sites:
Center for Reproductive Biology http://www.crb.wsu.edu/
WSU Research News and Features: http://researchnews.wsu.edu/