Estrogen in rivers may target fish hearts

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By Brian Bienkowski
Staff Writer
Environmental Health News

Feb. 4 , 2014

Estrogenic compounds in rivers may have a newly discovered target: the developing hearts of fish.

Chemicals that mimic estrogen in waterways have been linked to a variety of effects on wildlife. But new research using water from several rivers in Virginia and Pennsylvania is the first to show that they attach to proteins that control how heart valves grow in fish.

“This tells us that endocrine-disrupting chemicals could lead to improper heart development. We were quite surprised since this is something that others hadn’t observed before,” said study co-author Luke Iwanowicz, a research biologist with the U.S. Geological Survey based in West Virginia.


Researchers exposed zebrafish embryos to water from 19 sites in the Susquehanna, Delaware, Allegheny and Shenandoah watersheds. Water from 16 of the sites triggered proteins in the fish that were estrogen receptors, so the rivers probably contained hormone-altering chemicals.

These receptors are attached to DNA, which turn genes on and off. While such activity is common in the liver, this is the first experiment to show estrogenic activity in heart valves.

Without analyzing the water, it’s not possible to link the heart valve findings to any specific chemical. In addition, the potential effects on the fish are unclear, said Tamara Tal, a postdoctoral fellow with the U.S. Environmental Protection Agency who studies zebrafish.

Many hormone-mimicking compounds are found in sewage effluent and runoff that flows into waterways. Included are natural estrogens in people’s urine, birth control pill hormones, soy, some pesticides and the plasticizer bisphenol A (BPA).

There are “literally thousands of chemicals in the water at low concentrations,” said Dan Gorelick, lead author of the study, which was published in the journal Environmental Health Perspectives, and an assistant professor at the University of Alabama.

“This tells us that endocrine-disrupting chemicals could lead to improper heart development.” –Luke Iwanowicz, USGS“We don’t know yet in this case what’s in the water, what the bioactive ingredient is,” Gorelick said. “But we know from the lab that if we add a synthetic estrogen like BPA, or a natural estrogen, both of those preferentially target the heart valves. It’s not as simple as one class [of estrogens] or another.”

The study is the latest using a novel test in which the cells of genetically engineered zebrafish turn fluorescent green when estrogen receptors are activated. Such research allows the researchers to see which cells respond to estrogens in embryos, and can give clues as to possible development problems spurred by estrogen exposure.

The fish were exposed to water from the rivers mixed with lab water, with dilution ranging from 1 part river water per 100 parts lab water, to 1 part per 4,000.

While most of the water samples activated estrogen receptors in both the heart valves and the liver, when the river water was more diluted, five of the samples activated them only in the heart valves, Gorelick said. Hormone-like chemicals often do not act in a typical way; they can have health effects at low doses but no effects or different effects at high doses.

Dan Gorelick

Water that triggered the receptors in the heart valves was from the Delaware River in Pennsylvania, and the Naked, Muddy and Linville creeks and Long Meadow Run in Virginia.

The American Chemistry Council, which represents chemical manufacturers, was skeptical that the findings show anything meaningful.

“The untested hypothesis of this study is that ‘the activation of estrogen receptors in heart valves during development leads to the intriguing hypothesis that estrogen signaling influences valve formation,’ ” Steve Hentges, a representative of the American Chemistry Council, said in a prepared statement. “If that is true, then similar to BPA, the stated hypothesis would also apply to genistein, a phytoestrogen commonly found in foods, such as soy, and also examined by these researchers,” he said.

Previous work by Gorelick showed that both BPA and genistein activate estrogen receptors in zebrafish hearts.

Gorelick agreed that that the potential effects are unknown. “Any relevance to fish or humans is potential, not actual, because the untested hypothesis is exactly that: untested,” said Gorelick, who performed the experiments as a post-doctoral student at the Carnegie Institution for Science in Baltimore.

The next step is breeding the zebrafish to see if there are any heart problems. The researchers also are trying to tease out which of the estrogen compounds in the water are targeting the heart valves.

“Any relevance to fish or humans is potential, not actual, because the untested hypothesis is exactly that: untested.” –Dan Gorelick, University of AlabamaKen Korach, a scientist at the National Institutes of Health who studies the response of human cells to estrogens, said the experiment probably doesn’t have much relevance for human health because the estrogen receptors in humans are different than in zebrafish.

“But even if you’re just concerned about zebrafish, this is only developmental embryonic exposure,” Korach said. “It would be interesting to see adult zebrafish exposures and whether they are affected in any way.”

Estrogen compounds previously have been linked to altered gene expression and reproductive problems in wildlife. In perhaps the most famous study, male fathead minnows became feminized and the entire population collapsed after a seven-year study in which researchers dosed an experimental lake area in Ontario, Canada, with a synthetic estrogen found in birth control pills.


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