A new study finds that two chemicals found in fungicides and pesticides caused fertility defects in male rats that were passed down to nearly every male in subsequent generations--an effect not seen with any other known toxin. The results support the notion that hormonelike pollutants could be causing reproductive problems in humans.

The work was led by reproductive biologist Michael Skinner of Washington State University in Pullman, whose lab has been studying vinclozolin, a fungicide used in the wine industry. Vinclozolin blocks cell receptors that are normally activated by the hormone androgen. It is just one of a suite of widely used chemicals, from flame-retardants to ingredients in plastics, that can cause reproductive abnormalities in lab animals.

When Skinner and his team injected vinclozolin into the abdomens of pregnant rats during a specific window early in pregnancy, the male offsprings' sperm counts dropped 20% compared to control mice. In addition, their sperm motility was 25% to 35% lower, and the cells within the testes underwent higher rates of apoptosis--a form of cell death. Subsequent generations of males had similar reproductive abnormalities and seemed to inherit the defect from their fathers--a result also seen in rats treated with methoxychlor, a pesticide used as a substitute for DDT.

That only male offspring were affected suggested that the two compounds had caused mutations in the male cell's germ line, the cells that give rise to sperm, says Skinner, whose team reports its results 3 June in Science. But because the vinclozolin-induced fertility changes occurred in almost every male rat descended from a treated mother rather than in a small percentage of offspring (as is seen in germ line mutations caused by radiation), Skinner suspects an epigenetic mechanism--a change that doesn't mutate the DNA sequence of an animal, but rather affects how genes are expressed. "The hazards of environmental toxins are much more pronounced than we realized," he says.

Other researchers are cautious. "These are remarkable observations. They are going to have a large impact on how we look at these kinds of chemicals" if they are reproducible, says Earl Gray, a toxicologist with the Environmental Protection Agency (EPA). "It's provocative," admits geneticist Robert Braun of the University of Washington, Seattle. "But I don't think we have a clue as to what's really happening."

According to EPA, the doses used in the experiment were much higher than EPA's limits on levels to which people can be exposed, and Gray says this single study won't change regulations for vinclozolin and similar antiandrogens. For now, "it's going to be very important for other people to look at this," he says.


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© 2005 by the American Association for the Advancement of Science.

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