The chemical, found in many plastic products, can interfere with normal brain development.
In a study published in the journal Proceedings of the National Academy of Sciences, researchers report that bisphenol A (BPA) may suppress genes that are critical to early development of the central nervous system, which may predispose both animals and humans to neurodevelopmental disorders.
People can absorb BPA when it seeps from plastic bottles or the lining of metal cans into the food or drinks we consume. In previous studies, higher levels of BPA in people’s urine have been linked to behavioral problems as well as reproductive disorders, heart disease and obesity, which prompted the Food and Drug Administration to ban the compound from baby bottles in 2012. In the current research, scientists from Duke Medicine in Durham, North Carolina tried to understand how BPA can harm health, and focused on its ability to interfere with developing nervous systems in both animals and humans.
As neurons start to form, chloride levels in cells are critical for guiding the nascent nerves to their proper place in the brain. Over time, as the neurons mature, chloride is pumped out of the cells by a chloride transporter called KCC2. If chloride levels remain high, the neural circuits don’t form and connect properly.
By exposing cell cultures of rat and human nerve cells to BPA, the researchers discovered that the chemical inhibits KCC2 from doing its job in lowering chloride levels.
“Chloride going from high to low around the time of birth, in a very choreographed manner, is an absolute prerequisite for the nerve cell to find its right place. That is perturbed by BPA,” says lead study author Dr. Wolfgang Liedtke, an associate professor of medicine and neurobiology at Duke. “If chloride is high, things go wrong. Nerve cells in the central nervous system are protecting themselves by pumping out chloride all the time.”
Although the researchers confirmed that both sexes are affected by the BPA, female neurons appear to be more susceptible to the compound’s damaging effects. “The process of emptying out chloride from the neuron is faster and more dynamic in females. This is likely at the root of that. BPA can attack the process more actively and potently in females,” says Liedtke.
In addition to exploring BPA’s effect on cell cultures, the researchers also studied the chemical in live animals–and found the same results. The scientists fed BPA to pregnant mice and studied the brain neurons in their offspring. “This showed us that what we studied in the dish happens in newborn mice and provides very important and exciting information,” says Leidtke.
The neurons in the newborn mice whose mothers were exposed to BPA showed changes in gene activity along stretches of DNA that are critical to lowering chloride levels. This so-called DNA methylation influences whether genes are expressed, or active, or not. “Methylation changes how the genetic code reads. In the mice, the BPA influenced the DNA methylation to the neurons of the brain that are supposed to form the cerebral cortex. [These are] the most long-lasting and can stay with the animals or humans for decades,” says Leidtke.
That legacy could also emerge as neurodevelopmental disorders later in life, which may be exacerbated by certain stresses or traumatic events. “I think we are allowed to speculate the effect of BPA might have on the susceptibility of an individual to misregulation of genes in response to developmental challenges such as puberty or menopause, or stresses or injuries such as traumatic brain injury,” says Leidtke. “Even regulatory challenges such as gaining weight. That is all possible with this documentation that BPA leads to DNA methylation and epigenetic chang.,”
Fortunately, there is hope that the changes are reversible. When the researchers treated the brain cells of mice whose mothers were exposed to BPA during pregnancy with a drug that corrects the methylation, they were able to compensate for the excessive levels of chloride in the cells. Hopefully, that means that if such interventions are used early enough, the damage to nerve development can be avoided too.
The findings seem to reinforce the dangers of BPA for human development; while the European Union banned the use of BPA, in the U.S., the FDA has only banned its use in baby bottles and cups, noting that the evidence is not conclusive enough to remove the chemical from all food packaging — yet. Leidtke hopes his team’s paper adds to the ongoing conversation about whether the current regulations protect consumers enough from the potential dangers of BPA exposure.