Effects of developmental bisphenol A exposure on reproductive-related behaviors in California mice (Peromyscus californicus): a monogamous animal model.

Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist-antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus), where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight) or ethinyl estradiol (EE) (0.1 part per billion) to provide a "pure" estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a consideration in risk assessment studies

Measurements of exploratory and anxiety-like behaviors in EPM.

<p>a) Time spent in the open arms of the EPM. No difference was evident in time spent in the open arms between BPA- and EE-exposed males compared to CTL California mice males. In contrast, CTL female California mice spent more time in the open arms than BPA-exposed females and CTL males. ^a,bDifferences between maternal diets within sex (P<0.05), and ^*differences between sexes within maternal diet (P = 0.05). b) Proportion of time spent in open arms, c) Time spent immobile, d) Total number of entries in all arms, e) Distance travelled, and f) Velocity. None of these other measurements were affected by sex or maternal diet.</p

Barnes maze search strategy.

<p>The graph depicts the usage of random (yellow), serial (green), and direct (black) search strategies by CTL, EE-, and BPA-exposed males and females. During the seven d trial period, there were no consistent differences in search strategy based on maternal diet or sex.</p

Measurement of territorial marking in BPA-exposed California mice males compared to CTL males.

<p>There was no difference on d 0 between BPA-exposed and CTL males, who did not have any visual or other sensory contact. When BPA-exposed and CTL males were placed in the same cage with a barrier between them, BPA-exposed males exhibited a trend to engage in less territorial marking on the first d of exposure (P<0.07) and even more so seven ds later than CTL males (*, P<0.003).</p

Measurements of latency (a and b) and error rate (c and d) in the Barnes Maze for California mice males and females.

<p>In males, developmental exposure to BPA or EE did not affect latency or error rate in the Barnes Maze compared to CTL males. Likewise, no effects were observed in BPA- or EE-exposed females compared to CTL females.</p

Body weight measurements of California mice males and females exposed to BPA, EE, and CTL diet.

<p>Measurements of body weight from 30 to 90 ds of age indicated that in males developmental exposure to BPA or EE did not affect body weight gain. In contrast, females exposed to EE weighed less than CTL females, EE males, and BPA females (P<0.05).</p