Teen mice exposed to low levels of BPA behave like opposite sex as adults, study finds.

What did they do?

Researchers from China's Zhejiang Normal University examined the effects of BPA exposure during adolescence on adult cognitive, activity and mood behaviors.

In the study, 32-day-old  male and female mice drank an oil solutions with varying amounts of BPA daily for eight weeks that contained resulting in daily doses of either 0, 40 (low) or 400 micrograms (high) of BPA per kilogram of body weight (µg/kg/day). (Correction 7/6/2011) This age of mice is similar to the time of development when humans enter puberty. The National Toxicology Program's current reference dose – a dose thought to have little health risk during a lifetime – for oral BPA exposure is 50 µg/kg per day.

Three days after exposure – at 90 days of age – all mice were tested on a variety of behavioral tasks that routinely show different performances between adult male and female mice. This age coincides with young adulthood in humans.

The open field task was used to test for activity, exploration (rearing on the back legs) and conflict (grooming) behaviors.

Anxiety-like behaviors were assessed in the elevated plus maze (EPM). The EPM is a plus-shaped maze with two open arms and two arms protected with walls, elevated 50 centimeters above the floor. Less anxious mice tend to spend more time in the open arms of the maze. Exploration is measured by the number of head dips on the open arms of the EPM.

Spatial memory – the ability to remember a specific location – was tested in the Morris water maze. The water maze consists of a circular pool filled with cloudy water. An escape platform is located just beneath the water’s surface in one section of the pool, and the ability for the mice to locate and remember the location of this hidden platform across subsequent days was recorded.

Lastly, mice were tested on the ability to learn not to step off a platform (step-down task) in order to avoid a mild shock.

Body weights were recorded before and after BPA exposure. Reproductive organ weights and levels of sex steroids were measured after behavioral testing.

What did they find?

Spatial memory in untreated mice showed a strong sex difference. The untreated male mice better remembered the location of the escape platform. Low dose BPA treatment reversed this effect. The ability of male mice to find the platform was impaired and resulted in a female-like performance on this task.

No sex difference was found in the performance of untreated mice on the step-down task. Interestingly, the males exposed to low dose BPA stepped down sooner than untreated males – an effect not seen in females – thereby producing a sex difference on the performance of this task.

Untreated male mice exhibited more exploratory behavior than female mice. BPA exposure at the low dose reversed this effect in male mice, producing female-like behavior. Head dips on the EPM (another measure of exploration) also showed a sex difference in the untreated animals: males had more head dips and thus explored more than females. Both low and high BPA exposures reversed this sex difference by affecting both males and females. Head dips increased in females and decreased in males.

An obvious sex difference in anxiety on the EPM was also measured. Untreated male mice entered and spent more time in the open arms of the maze than untreated female mice. This sex difference was eliminated after low and high BPA treatment. After the exposures, female mice exhibited less anxious behavior – they spent more time in the open arms – while male mice exhibited more anxious-like behavior – they spent less time in the open arms.

Eight weeks at both low and high BPA exposures reduced male body weight when compared to unexposed males. The lower exposure also reduced female body weight. No differences were measured in sex steroid levels or weights of reproductive organs.

What does it mean?

Exposure to low and high levels of BPA during adolescent development can alter adult behaviors of male and female mice.

This research is unique in that it shows that long-term dietary BPA exposure beginning in adolescence can shift the characteristic male/female sex differences in some behaviors. The overall results found a reduction or reversal in some behaviors relative to those displayed by untreated male and female mice. In some key areas – namely memory and exploration – males behaved more like females. In others, females took on male behavioral patterns.

The altered behavior patterns raise concerns about people ingesting BPA during adolescence. To date, no studies have addressed the health concerns of human exposures to BPA during this transitional period of development.

Based on the study's findings, it appears that adolescence is a period of brain development that is sensitive to BPA. The reported effects resemble the behavioral changes seen with fetal and early life exposures in rodents. Most importantly, the low-level exposure used here suggests the brain is especially sensitive to the EDC properties of this chemical.

The BPA exposures altered spatial memory performance of male mice. Traditionally, male rodents outperform females in spatial navigation tasks. A similar sex difference is seen in humans on spatial navigation tasks as well (Driscoll et al. 2005). These effects parallel the shift in male performance seen following BPA exposure during pregnancy and early life (Xu et al. 2010), and suggest some memory behaviors are more susceptible to this EDC in males than females.

Treatments also reversed the difference in anxiety-like behavior, resulting in more anxious activity in males and less anxious activity in females. BPA exposure also erased the sex-difference on exploratory behaviors in mice. Therefore, this EDC may interfere with hormonal organization during adolescence on brain development underlying exploratory and emotional behaviors.

The central nervous system is sensitive to the effects of industrial chemicals, especially during significant periods of development. These outcomes suggest BPA can alter the the way hormones influence brain development, possibly by interfering with the organization of specific brain circuits (Hajszan and Leranth 2010).

The results of this animal study are a first step to understanding how BPA may influence human health. Exposure to the chemical is ubiquitous; allmost all people in the United States have BPA in their bodies, according to a recent Centers for Disease Control report. Significant sources of BPA exposure in humans during the transitional teenage period include food, such as soft drinks and canned foods (von Goetz et al. 2010), and the exposure levels used in this study are well within the range humans can be exposed to.