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Washington State University professor Michael Skinner and colleagues have gathered compelling evidence on how exposure to the widely used fungicide, Vinclozolin, can harm not only those who are directly exposed to this environmental toxin, but also their offspring. This study shows that the deleterious effects of one generation's exposure to toxic chemicals can be passed down to future generations by changing the way an organism's genes function.
The work reveals a new mechanism for inheritance of traits--a novel mechanism much faster than DNA mutation alone.
Though this study revolutionizes the way science defines evolution, it also cautions us on the conservation front. The results show that detrimental effects from environmental pollutants could be passed down to many future generations, failing to be washed out over time.
This change in gene function, without a change in genetic make-up, is called an epigenetic change. Epigenetic changes can be caused by physically preventing a gene from working as it normally would, that is, preventing a gene from being turned on (expressed) or turned off (not expressed). Epigenetic effects inhibiting or stimulating gene expression can cause the gene to produce too much or too little of the product it codes for. Products of gene expression include proteins such as hormones, which can influence various behaviors, or even the production of more cells.
The epigenetic effects can be achieved by attaching a chemical structure called a methyl group to part of the DNA called a base-pair. This process is called methylation. The pattern of methylation on genes can be influenced by what's happening in an organism's surrounding environment.
"The dogma of evolution states that DNA sequence mutation leads to heritable good or bad qualities," says Skinner. "Our study shows that heritable epigenetic effects could have serious influences on evolutionary biology.”
The frequency of epigenetic effects is often several times more likely than the incidence of DNA mutations. Skinner and colleagues discovered that when they injected the fungicide Vinclozolin into the abdomens of pregnant rats during the period of a fetus' sex determination, 90 percent of male offspring exhibited increases in sperm cell death and decreases in sperm number and motility. It should be noted that Vinclozolin exposure has also been implicated as a possible mediator of decreases in human sperm count.
Interestingly, when the male offspring from Vinclozolin-treated mother rats were bred to female offspring of Vinclozolin-treated and non-Vinclozolin-treated mothers, their male offspring also showed statistically significant changes in sperm function compared to control animals and their offspring. This pattern continued through four generations of male rats. It was also determined that this effect was passed on through generations by males (brothers and fathers) only.
To determine if this large incidence of sperm dysfunction was being passed down from generation to generation by an epigenetic mechanism, researchers explored the molecular makeup of treated and non-treated rats to look for differences in methylation patterns.
The results showed that offspring of Vinclozolin-treated mothers had higher rates of methylation in genes compared to those of controls, suggesting an epigenetic mechanism.
"We will be working on a dose-response study to determine if the amounts of Vinclozolin found in the environment have similar effect to the high levels of Vinclozolin injections in the present study," says Skinner. "But first we're concentrating on the molecular aspects."
The scientists hope to study methylation patterns in order to make a map of possible epigenetic markers. These markers can then be used to determine if methylation has occurred in humans and other species in response to environmental changes. "We hope to use our molecular work to determine methylation patterns and use them as a diagnostic tool,” says Skinner. "This could offer a new paradigm on how we study the development of disease."
Sara O'Brien obtained a B.S. in animal science and a M.S. in integrative biology from the University of Illinois, and is presently pursuing a doctorate in zoology at the University of Washington, studying the neuroendocrine control of reproduction in birds.
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Epigenetics refers to a process in which the function of the genetic code is changed because chemical groups attach to the DNA and physically block specific regions of genetic code from being expressed. An epigenetic change is not considered a mutation because it does not change the genetic code itself, that is, the sequence of base pairs in the DNA. Chemical structures called methyl groups can block regions of genetic code and cause epigenetic effects. These patterns of methylation are often influenced by changes in an organism's environment. Schematic: Sara O'Brien
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