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Zebrafish study shows bisphenols affect embryonic brain development

Researchers find low levels of chemicals linked to hyperactivity in exposed fish
January 13, 2015

Deborah Kurrasch, a researcher in the University of Calgary’s Cumming School of Medicine, has shown that BPA and BPS cause alterations in brain development that can lead to hyperactivity in zebrafish. Photo by Riley Brandt, University of Calgary

University of Calgary researcher Hamid Habibi, left, and Cassandra Kinch, worked alongside Kurrasch on the BPS study. Photo by Riley Brandt, University of Calgary

Bisphenol A, known as BPA, is a chemical produced in massive quantities around the world for use in consumer products, including household plastics. In response to public concerns, many manufacturers have replaced BPA with a chemical called bisphenol S (BPS), which is often labelled as “BPA-free” and presumed to be safer.

In a study published Monday in the Proceedings of the National Academy of Sciences (PNAS), researchers in Deborah Kurrasch’s lab at the University of Calgary have provided evidence that BPA and BPS cause alterations in brain development leading to hyperactivity in zebrafish.

“I was actually very surprised at our results. This was a very, very, very low dose, so I didn’t think using a dose this low could have any effect,” says Kurrasch, PhD, a researcher in the University of Calgary’s Cumming School of Medicine and corresponding author on the paper.

For the study, Kurrasch worked with University of Calgary researcher Hamid Habibi, PhD, and Cassandra Kinch, a PhD student, to expose zebrafish embryos to concentrations of the chemicals at levels found in the Bow and Oldman rivers of southern Alberta. By doing this, exposure to BPA and BPS changed the timing when neurons were formed in the brains of the zebrafish.

Prenatal period a particularly sensitive stage

“These findings are important because they support that the prenatal period is a particularly sensitive stage, and reveals previously unexplored avenues of research into how early exposure to chemicals may alter brain development,” says Kinch.

“In the second trimester, brain cells become the specialized neurons that make up our brain. What we show is that the zebrafish exposed to BPA or BPS were getting twice as many neurons born too soon and about half as many neurons born later, so that will lead to problems in how the neurons connect and form circuits,” says Kurrasch, a member of the Alberta Children’s Hospital Research Institute and the Department of Medical Genetics.

Change in behaviour detected

Researchers discovered the number of neurons generated in the developing zebrafish brains increased by 180 per cent compared with unexposed fish. They also learned that BPS increased the number of neurons by 240 per cent in similar experiments. The result was a change in behaviour, with the fish demonstrating greater hyperactivity later in life.

Another surprise finding was that zebrafish receptors targeted by BPA and BPS to mediate this early neuronal birth in zebrafish brains were androgen receptors. Assumptions based on numerous reports postulated that BPA and BPS modulate normal physiology by mimicking the endogenous sex steroid estrogen, and not testosterone.

“Finding the mechanism linking low doses of BPA to adverse brain development and hyperactivity is almost like finding a smoking gun,” says Habibi, a professor of environmental toxicology and comparative endocrinology in the Faculty of Science.

A caution for pregnant women

Although further research is needed to explore that link and the potential effect on human brains developing in the womb, Kurrasch says the findings add weight to other studies suggesting pregnant women should try to limit their exposure to items containing bisphenols. The evidence also supports removing all bisphenols and structurally similar chemicals from consumer products, she says.

Zebrafish are a widely accepted biomedical model for understanding embryonic brain development. About 80 per cent of the genes found in people have a counterpart in zebrafish — and possess very similar developmental processes as humans.

The study was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC).