Transgenerational effects of prenatal bisphenol A on social recognition

Abstract

Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders.

Keywords: Attention deficit hyperactivity disorder; Autism; Endocrine disrupting chemicals; Epigenetics; Social recognition; Transgenerational inheritance.

Figure 1

Mean +/− SEM time in seconds spent investigating an ovariectomized adult mouse during a social recognition task. In panels A and B, circles and solid lines represent control mice, black for male and white for female data. BPA animals' data are in triangles with dashed lines. As with controls, male symbols are black and female symbols are white. Panels A and B show time spent investigating on each trial, including the last, when a novel stimulus mouse was presented. A) Juvenile (PN22) male and female F1 mice were exposed to control (n=15 males and n=10 females) or BPA supplemented diet during gestation (n=14 males and n=12 females). B) F1 mice were mated to the third generation to create F3 control (n=9 males and n=8 females) and F3 BPA lineage mice (n=7 males and n=8 females). In panels C and D, male data are presented in black and female data are in gray histograms. These histograms show the sum of all time spent investigating the female during the habituation phase in the C) F1 and D) F3 generation juvenile mice. * Significant main effect of diet, p<0.05. ** Significant difference between trial 8 (familiar mouse) and 9 (novel mouse), p<0.05. ***Significant diet effect, only control mice had a significant increase in investigation between trials 8 and 9, p<0.05.

Figure 2

Mean +/− SEM number of lines crossed in the open field. Data from males are presented in black histograms and females are in gray. A, C, E) F1 juvenile (PN23–24) control (n=8 males and n=9 females), BPA supplemented diet (n=8 males and n=8 females) mice. B, D, F) F3 juvenile control (n=6 males and n=7 females) and BPA lineage (n=6 males and n=7 females) mice. In panels A and B are numbers of lines crossed in the center zone. In C and D are numbers of lines crossed in the outer zone. Panels E and F show total numbers of line crossed in the entire apparatus. There were no effects of diet or sex in the F1 mice. *Significant difference between BPA and control lineages, p<0.05.

Figure 3

Mean +/− SEM of time spent investigating water and male urine in an odor discrimination task. In panel A, circles and solid lines represent control lineage mice, black for male and white for female data. BPA lineage data are in triangles with dashed lines. As with controls, male symbols are black and female symbols are white. A) Time in seconds spent investigating water (trials 1–3) and male urine from two different pools (trials 4–6 and 7–9). F3 adult mice: control (n=5 males and n=6 females) and BPA lineage mice (n=6 males and n=6 females) were tested. B) Total time investigating male urine summed from trials 4–9 in control and BPA lineage mice. In all groups we noted a significant difference between * trial (trials 4 and 7) as compared to all other trials, p<0.05.