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BPA study shows gender effects in mice

plastic bottles

Public health issue: BPA-free water containers and plastics are increasingly popular as concern grows about the chemical's impact(Source: iStockphoto)


The study by scientists from Columbia University also shows BPA exposure induces persistent, sex-specific and dose-dependent changes in social behaviours, such as frequency of sniffing, chasing, and aggression.

But other scientists debate whether or not the findings, published in today in Proceedings of the National Academy of Sciences, can be extropolated to humans.

Bisphenol A, or BPA, is a common ingredient used in household plastics and can be found in the lining of canned foods, some plastic containers and cashier receipts. It has previously been associated with a range of neurological and hormonal effects in laboratory studies.

Professor Frances Champagne and colleagues exposed pregnant mice to multiple doses of BPA, including exposures below the level that is considered "safe" for humans.

"Low-dose, prenatal BPA exposure induces lasting epigenetic disruption in the brain that possibly underlie enduring effects of BPA on brain function and behaviour," they conclude.

For example, male mice became less likely to chase other mice as the BPA dose increased, and both male and female mice showed an increase in aggressive behaviour with increasing BPA doses.

Males also showed a decrease in sniffing behaviours at higher doses, but were more likely to travel further around the cage with increasing doses of BPA.

The study also shows clear gender differences in the impact of BPA on the expression of genes associated with regulation of oestrogen receptors in the brain.

More research needed

Experts in the field say the findings highlight the need for further research.

Toxicologist Emeritus Professor Michael Moore from the University of Queensland says the study raises almost as many questions as it answers, showing some perplexing J-shaped and U-shaped curves in the effects of BPA according to dose.

"As soon as you've got a J-shaped curve, that's basically saying that notionally, at zero concentrations you have a certain effect and these effects decrease as you go down to a certain point, and then increase again," Moore says.

For example, in the case of aggressive behaviour, a zero dose of BPA had the same effect on the frequency of aggressive behaviour as a BPA dose just under 200 micrograms.

However Moore says the epigenetic effects of BPA -- effects on gene expression -- are important.

"What they're basically saying is these impacts on DNA methylation have a consequence in the gene expression, that is going from the DNA through the mRNA to the production of the enzyme itself, and in many cases, people have not followed that process, so that's quite a powerful argument about effect."

Not possible to extrapolate

Professor Richard Sharpe, from the MRC Centre for Reproductive Health at the University of Edinburgh, says the results are unlikely to be extrapolated to humans for a number of reasons.

The lowest dose used by the Columbia team is still 10-20 times higher than normal human bisphenol A exposure; there is huge between-animal variation in effect; and there is no information about the reproducibility of the results, says Sharpe.

If the effects described work through an oestrogen mechanism, "they are unlikely to be human relevant," he adds.

This is because pregnancy levels of oestrogens in humans are far higher than in mice and would swamp any weak oestrogenic effects of bisphenol A.
