The latest research from the University of Missouri on bisphenol A shows that the ubiquitous chemical causes male deer mice to become “demasculinized,” leading scientists to conclude that exposure during human development could be damaging to behavioral and cognitive traits that are important in reproduction.
The MU research demonstrated a link between bisphenol A, or BPA, and severe problems with spatial navigation abilities in captive male deer mice, said Cheryl Rosenfeld, associate professor in biomedical sciences in the College of Veterinary Medicine and investigator in the Bond Life Sciences Center.
Studies by other researchers have demonstrated that males of polygynous species — one male breeding with several females — tend to possess enhanced spatial navigation abilities compared to females. In the wild, spatial navigation skills are crucial to males of polygynous species like deer mice because it allows them to find mates that are dispersed throughout the environment.
“The BPA-exposed deer mice in our study look normal; there is nothing obviously wrong with them,” Rosenfeld said. “Yet, they are clearly different. Females do not want to mate with BPA-exposed male deer mice, and BPA-exposed males perform worse on spatial navigation tasks that assess their ability to find female partners in the wild.”
The research will be published in the Proceedings of the National Academy of Sciences. Rosenfeld collaborated with David Geary MU Curators’ Professor of Psychological Sciences, and Todd Schachtman, professor from the Department of Psychological Sciences. The primary author was a graduate student in the MU Interdiscplinary Neurosciences Program, Eldin Jašarević, who conducted most of the experiments.
A known endocrine disruptor, BPA has been found to mimic the female hormone estrogen, which can lead to a range of effects in both humans and animals.
“We know that the active form of BPA binds to our steroid receptors, meaning it can affect estrogen, thyroid and testosterone function,” Rosenfeld said. “It might also cause genetic mutations. Thus, this chemical can hinder our ability to reproduce and possibly cause behavioral abnormalities that we are just beginning to understand.”
The findings set the stage for researchers to examine how the chemical might impact the behavioral and cognitive patterns of boys versus girls. “Our study could suggest that boys may be more susceptible (to BPA exposure) than girls would be,” Rosenfeld said.
It is not known yet if BPA exposure affects human spatial navigation skills. As with mice, boys are typically more adept at this skill than girls. According to a 1992 Indiana study, boys exposed while in the womb to a different endocrine disruptor — diethylstilbestrol (DES), a potent estrogen — exhibit spatial navigational defects, compared to boys whose mothers did not take this compound. In the mid-twentieth century, before DES was banned, physicians routinely prescribed it to prevent miscarriages.
As for BPA possibly inducing similar effects, Rosenfeld said other researchers should be on the lookout. Some scientists are already tracking children affected by BPA, so they might want to measure these children’s spatial navigation abilities, their learning and memory abilities, and their overall behavior patterns over time, she said.
In the recent study, female deer mice were fed BPA-supplemented diets two weeks prior to breeding and throughout lactation. The mothers were given a dosage equivalent to what the U.S. Food and Drug Administration considers non-toxic and safe for mothers to ingest. At weaning (25 days of age), the deer mice offspring were placed on a non-supplemented BPA diet. When the mice became sexually mature, researchers tested each mouse’s ability to navigate a maze. Each animal had two five-minute opportunities per day, for seven days, to try to find its way into a home cage through one of several holes placed around the edge of an open maze marked with visible navigational cues. Many male mice that had been exposed to BPA early in their development never found the correct exit.
By comparison, male mice that had not been exposed to BPA consistently found the hole leading to their home cage within the time limit, some on the first day. Moreover, the untreated mice quickly learned the most direct approach to finding the correct hole, while the exposed males appeared to employ a trial and error strategy, Rosenfeld said.
In addition, male deer mice exposed to BPA were less desirable to female deer mice. Females primed to breed were tested in a so-called mate choice experiment. The females’ level of interest was measured by observing specific preferential behaviors, such as nose-to-nose sniffing and the amount of time the female spent evaluating her potential partner. Rosenfeld said that both non-exposed and BPA-exposed females favored control males over BPA-exposed males on a two-to-one basis.
“These findings presumably have broad implications to other species, including humans, where there are also innate differences between males and females in cognitive and behavioral patterns,” Rosenfeld said. “In the wide scheme of things, these behavioral deficits could, in the long term, undermine the ability of a species such as the deer mouse to reproduce in the wild. Whether there are comparable health threats to humans remains unclear, but there clearly must be a concern.”
More than 8 billion pounds of BPA are produced every year, and more than 90 percent of people in the United States have measurable amounts of BPA in their bodies. Exposure to BPA is primarily through diet because many plastic and paper containers used to store food are formulated with the chemical.
However, in a recent study, Rosenfeld found that exposure to BPA through diet has been underestimated by previous lab tests. In that study, funded by the National Institute of Environmental Health and Sciences, researchers compared BPA concentrations in mice that were given a steady diet supplemented with BPA throughout the day, compared to the more common lab method of single exposure, and found an increased absorption and accumulation of BPA in the blood of mice.
“We believe that these mouse model studies where the BPA exposure is through the diet is a more accurate representation of what happens to BPA as the human body attempts to processes this toxic substance,” said Rosenfeld. “When BPA is taken through the food, the active form may remain in the body for a longer period of time than when it is provided through a single treatment, which does not reflect the continuous exposure that occurs in animal and human populations. We need to study this further to determine where the ingested BPA becomes concentrated and subsequently released back into the bloodstream to be distributed throughout the body.”