Pesticides Cause Lasting Damage to Rat Sperm

Finding could have implications for humans, study suggests

THURSDAY, June 2, 2005 (HealthDay News) -- Pregnant rats exposed to environmental toxins gave birth to four generations of males with decreased sperm function, a new study reports.

It's not clear what these findings mean for humans, but the researchers aren't discounting the potential significance.

"It's not a large leap to show that similar things could be happening in humans, but we need to show it," said Michael K. Skinner, senior author of the study and a professor of molecular biosciences and director of the Center for Reproductive Biology at Washington State University, in Pullman, Wash.

Perhaps more important, the findings also show that one exposure to an environmental toxin can generate permanent effects evident in several subsequent generations of rats -- and possibly other species, including humans, Skinner said.

"If a pregnant woman is exposed to that environmental toxin during mid-gestation, it could actually cause a disease state in adult offspring which is heritable," he explained. "It looks like male sperm is being affected and permanently reprogrammed."

The study appears in the June 3 issue of the journal Science.

Dr. Frederick Licciardi, associate director of reproductive endocrinology at New York University Medical Center, said there was no reason for humans to be unduly alarmed, but the various implications of the new findings were significant.

"Just the fact that there might be ways to epigenetically change the fetus from generation to generation by something that happens with the female rat or human is also interesting," he said.

Added Shanna Swan, a professor in the department of obstetrics and gynecology at the University of Rochester School of Medicine and Dentistry: "As a reproductive and environmental epidemiologist, this seems extremely important, because it may provide a mechanism to account for rapid changes in reproductive parameters over time (such as decreases in sperm concentration) which have been so puzzling."

Various environmental toxins, as well as radiation and chemotherapy, can cause genetic and development defects in offspring if a mother is exposed while pregnant. These changes are usually changes in DNA sequence and affect only one generation, the study researchers said.

To have an effect over more than one generation of offspring, the change needs to be an "epigenetic" one, meaning there is a chemical modification of the DNA.

For this study, the researchers exposed pregnant female rats to vinclozolin, a fungicide used heavily in the wine industry, and methoxychlor, a pesticide which is used as a DDT replacement. Both are endocrine -- or hormone -- disruptors.

The exposure took place at the time when gender was being determined and the testes and ovaries being developed.

Sperm numbers were reduced 20 percent and sperm motility about 25 percent to 35 percent for the rats exposed to vinclozolin. Similar effects were seen with methoxychlor. Ninety percent of all males in the next four generations experienced permanent changes in their DNA, Skinner said.

"That kind of a frequency cannot be attributed to a genetic mutation involving DNA sequence so it's epigenetic," Skinner explained. "We've changed that imprint."

The rats were exposed to higher doses of the toxins than humans would normally get in the environment. "We can't claim anything about the toxicology of the compounds for the human population," Skinner said. "We now need to go back and do the dose curves."

"The dose used was 200 milligrams per kilogram, which is just an unrealistic exposure as far as humans would expect," Licciardi added.

But there are implications beyond the impact of a specific toxin on a specific animal.

"We now need to think about how diseases develop. Epigenetics could be a major factor we didn't previously appreciate," Skinner said. "We need to evaluate environmental factors as a factor in evolutionary biology. It may explain why certain subpopulations evolve differently. This issue has a broader impact than just fertility."

More information

To learn more about infertility, visit the American Society for Reproductive Medicine.

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