Pollution fallout: are unattractive males Great-gram's fault?

A new study of mate preferences in rodents raises the prospect that pollutant exposures can have behavioral repercussions that persist generation after generation. In the experiment, female rats shunned males whose grandfathers had been exposed in the womb to a fungicide used on fruit crops.

Though brief, the vinclozolin exposures occurred when the fetal males' reproductive organs were developing. The laboratory doses were "four- to fivefold higher than you might expect to see in the environment," notes Michael K. Skinner of Washington State University in Pullman. Some farm workers might incur similar doses, he says.

The fungicide, known as a hormone mimic, prevents male-sex hormones from binding to cells (SN: 7/2/94, p. 15).

The hormones then can not correctly program gene activity in the male fetus' reproductive organs. Reproductive tissues in fetal females appear unaffected.

Skinner's team reported 2 years ago that although neither the animals nor their descendants encountered the fungicide again, all the males exposed in utero developed cancers and other diseases in middle age, as did all their male descendants.

The vinclozolin exposure didn't cause mutations, notes evolutionary biologist David Crews, who led the new study with neuroscientist Andrea C. Gore, both at the University of Texas at Austin. The fungicide instead altered regulatory switches--methyl groups that can bind to DNA--thereby misprogramming some unidentified genes that later become inappropriately active or inactive. Scientists refer to methylation of DNA as an epigenetic influence.

The new study examined 24 young-adult rats, 12 male and 12 female, provided by Skinner. Half of the animals had a grandfather that had been exposed prenatally to the fungicide.

Crews and Gore designed tests to see whether fungicide exposure in a previous generation influences an animal's attractiveness as a mate. They presented each individual with two opposite-sex rats at a time--one from an unexposed line, the other from a vinclozolin-affected line. The researchers measured how long the test animal spent in the area closest to each of the opposite-sex rats. Wire screens separated the animals.

Regardless of their exposure history, males distinguished between females from the fungicide-exposed or the clean line. However, after briefly checking out pairs of males, females from both groups spent most of their time hovering near the males from the unexposed line. To the researchers, all the males appeared healthy.

A report of the study was posted online this week for publication in an upcoming Proceedings of the National Academy of Sciences.

The team suspects that epigenetic changes, triggered by the fungicide two generations back, altered the males' scent signals. However, Crews' team also recently identified epigenetic changes in the brains of the vinclozolin descendants.

Reproductive biologist Frederick vom Saal of the University of Missouri-Columbia calls the behavioral findings "scary stuff." Scientists hadn't expected parents' lifelong collection of epigenetic changes to reach the next generation. "What's interesting," vom Saal says, is that "a fetus may escape normal deprogramming" that wipes clean the epigenetic record.

"That it even impacts behavior," he adds--"that's wild."

The new finding also suggests that cleaning up a polluted area may not erase its impacts on exposed populations, vom Saal says.

"It is all pretty remarkable--and novel" agrees L. Earl Gray Jr., a reproductive toxicologist with the U.S. Environmental Protection Agency in Research Triangle Park, N.C. However, he adds that he and his colleagues have reservations because the sample size is so small and the animals in each group came from just two litters.

Gray says that if the finding is confirmed in a larger group of unrelated animals, it would have major implications.