Washington State University Study Points to Role of Toxins in Inherited Disease
PULLMAN, Wash. -- A disease you are suffering today could be a
result of your great-grandmother being exposed to an environmental
toxin during pregnancy.
Researchers at Washington State University reached that remarkable
conclusion after finding that environmental toxins can alter the
activity of an animal's genes in a way that is transmitted through
at least four generations after the exposure. Their discovery
suggests that toxins may play a role in heritable diseases that
were previously thought to be caused solely by genetic mutations.
It also hints at a role for environmental impacts during
evolution.
"It's a new way to think about disease," said Michael K. Skinner,
director of the Center for Reproductive Biology. "We believe this
phenomenon will be widespread and be a major factor in
understanding how disease develops."
The work is reported in the June 3 issue of Science Magazine.
Skinner and a team of WSU researchers exposed pregnant rats to
environmental toxins during the period that the sex of their
offspring was being determined. The compounds - vinclozolin, a
fungicide commonly used in vineyards, and methoxychlor, a pesticide
that replaced DDT - are known as endocrine disruptors, synthetic
chemicals that interfere with the normal functioning of
reproductive hormones.
Skinner's group used higher levels of the toxins 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.
Further work will be needed to determine whether lower levels have
similar effects.
Pregnant rats that were exposed to the endocrine disruptors
produced male offspring with low sperm counts and low fertility.
Those males were still able to produce offspring, however, and when
they were mated with females that had not been exposed to the
toxins, their male offspring had the same problems. The effect
persisted through all generations tested, with more than 90 percent
of the male offspring in each generation affected. While the impact
on the first generation was not a surprise, the transgenerational
impact was unexpected.
Scientists have long understood that genetic changes persist
through generations, usually declining in frequency as the mutated
form of a gene gets passed to some but not all of an animal's
offspring. The current study shows the potential impact of
so-called epigenetic changes.
Epigenetic inheritance 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.
Epigenetic changes have been observed before, but they have not
been seen to pass to later generations.
While this research focused on the impact of these changes on male
reproduction, the results suggested that environmental influences
could have multigenerational impacts on heritable diseases.
According to Skinner, epigenetic changes might play a role in
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.
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 in part by a
grant to Skinner from the U.S. Environmental Protection Agency's
STAR Program.
Related Web sites:
WSU Center for Reproductive Biology http://www.crb.wsu.edu/
Michael Skinner's Web site: www.skinner.wsu.edu
WSU Research News and Features: http://researchnews.wsu.edu
Contact:
Michael Skinner, Center for Reproductive Biology, 509/335-1524,
skinner@wsu.edu
Cherie Winner, WSU News Service, 509/335-4846, cwinner@wsu.edu
James Tinney, WSU News Service, 509/335-8055, jltinney@wsu.edu