Effects of endocrine-disrupting chemicals on hypothalamic oxytocin and vasopressin systems.

Exposures to endocrine disrupting chemicals (EDCs) perturb hormonal systems. EDCs are particularly problematic when exposure happens in the fetus and infant due to the high sensitivity of developing organisms to hormone actions. Previous work has shown that prenatal polychlorinated biphenyl (PCB) exposure disrupts hypothalamic development, reproductive physiology, mate preference behavior, and social behaviors in a sexually dimorphic manner. Based on evidence that EDCs perturb social behaviors in rodents, we examined effects of PCBs on the neuropeptides oxytocin (OXT) and vasopressin (AVP) that are involved in regulating these behaviors. Rats were exposed prenatally (gestational days 16 and 18) to the weakly estrogenic PCB mixture Aroclor 1221 (0.5 or 1 mg/kg), to estradiol benzoate (EB, a positive control), or to the vehicle (3% dimethyl sulfoxide). In adult (~P90) brains, we counted immunolabeled oxytocin and vasopressin cell numbers in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. EDCs did not change absolute numbers of oxytocin or vasopressin cells in either region, although there were some modest shifts in the rostral-caudal distribution. Second, expression of genes for these nonapeptides (Oxt, Avp), their receptors (Oxtr, Avpr1a), and the estrogen receptor beta (Esr2), was determined by qPCR. In the PVN, there were dose-dependent effects of PCBs in males (Oxt, Oxtr), and effects of EB in females (Avp, Esr2). In the SON, Oxt, and Esr2 were affected by treatments in males. These changes to protein and gene expression caused by prenatal treatments suggest that transcriptional and posttranscriptional mechanisms play roles in mediating how EDCs reprogram hypothalamic development.

Application of a novel social choice paradigm to assess effects of prenatal endocrine-disrupting chemical exposure in rats (Rattus norvegicus).

Endocrine-disrupting chemical (EDC) exposures during critical periods of gestation cause long-lasting behavioral effects, presumably by disturbing hormonal organization of the brain. Among such EDCs are polychlorinated biphenyls (PCBs), a class of industrial chemicals. PCB exposure in utero leads to alterations in mating behaviors and other sexually dimorphic social interactions in rats. Many of the previous studies on social behavior gave the experimental animal a single or binary choice. This study applied a more complex behavioral apparatus, an X-shaped Plexiglas apparatus (FourPlex), that enabled an experimental animal exposed to PCBs or a vehicle to distinguish and choose among 4 stimulus animals of the same or opposite sex, and of different hormonal status. We found that rats were able to differentiate among the stimuli in the FourPlex and showed the expected preference for an opposite sex, hormone-treated rat, particularly for behaviors conducted in proximity. Prenatal treatment caused subtle shifts in behavior toward stimulus rats in the FourPlex; more robust effects were seen for the sexual dimorphisms in behavior. Importantly, the results differ from our previous results of a simple binary choice model, showing that how an animal behaves in a more complex social paradigm does not predict the outcome in a simple choice model, and vice versa. (PsycINFO Database Record

The effects of prenatal PCBs on adult social behavior in rats.

Endocrine disrupting chemical (EDC) exposures during critical periods of development may influence neuronal development and the manifestation of sexually dimorphic sociability and social novelty behaviors in adulthood. In this study, we assessed the effects of gestational exposure to PCBs on the social behavior of males and females later in adulthood. A weakly estrogenic PCB mixture, Aroclor 1221 (A1221, 0.5 or 1mg/kg) was administered to pregnant Sprague-Dawley rat dams. Both a positive control (estradiol benzoate; EB, 50µg/kg) and negative control (dimethylsulfoxide; DMSO in sesame oil vehicle) were similarly administered to separate sets of dams. The sexes responded differently in two tasks essential to sociality. Using a three-chamber apparatus that contained a caged, same-sex, gonadectomized stimulus animal and an empty stimulus cage, we found that both sexes showed a strong preference for affiliating with a stimulus animal (vs. an empty cage), an effect that was much more pronounced in the males. In the second task, a novel and a familiar stimulus animal were caged at opposite ends of the same apparatus. Females displayed a higher degree of novelty preference than the males. During both tests, females had significantly higher social approach behaviors while male engaged in significantly more interactive behaviors with the conspecific. Of particular interest, males born of dams that received prenatal A1221 (0.5mg/kg) exhibited an overall decrease in nose-to-nose investigations. These behavioral data suggest that the males are more sensitive to A1221 treatment than are females. In addition to behavioral analysis, serum corticosterone was measured. Females born of dams treated with A1221 (0.5mg/kg) had significantly higher concentrations of corticosterone than the DMSO female group; males were unaffected. Females also had significantly higher corticosterone concentrations than did males. Overall, our results suggest that the effects of gestational exposure to PCBs on adult social behavior are relatively limited within this particular paradigm.