The effects of prenatal PCBs on adult social behavior in rats

Abstract

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 1 mg/kg) was administered to pregnant Sprague-Dawley rat dams. Both a positive control (estradiol benzoate; EB, 50 μg/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 (0.5 mg/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 (0.5 mg/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.

Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero

“…Also, the same rats used in our current study were assayed for circulating corticosterone in a terminal blood sample. Interestingly, females treated with A1221 (0.5), but not males of either dosage, showed increased circulating corticosterone (Reilly et al, 2015). This suggests that the anxiety phenotype of the males in the current study may be due to a different neural substrate other than hypothalamic CRH neurons.…”

“…Results on tests of sociability and social novelty have been published (Reilly et al, 2015). Tests of sexuality (mate preference and ultrasonic vocalizations) are still under analysis (manuscript under preparation).…”

“…PCB exposure late in fetal development altered developmental milestones (Dickerson et al, 2011a) and affected adult sexual (Chung et al, 2001; Colciago et al, 2009; Steinberg et al, 2007a, 2008) and social (Reilly et al, 2015) behaviors. Moreover, PCBs changed levels of neurotransmitters and their receptors in the brain, including those involved in anxiety and affective states.…”

Two-hit exposure to polychlorinated biphenyls at gestational and juvenile life stages: 2. Sex-specific neuromolecular effects in the brain

“…While banned in the 1970s, recent epidemiological data show that PCB body burdens continue to be associated with impaired reproductive and neurobiological health in humans (Boucher et al, 2009; Buck Louis et al, 2013; Engel and Wolff, 2013). In addition, rodent studies demonstrate that PCBs exert subtle but chronic effects on a range of social and anxiety related behaviors (Elnar et al, 2012; Jolous-Jamshidi et al, 2010; Reilly et al, 2015; Tian et al, 2011). Many of these behaviors are sexually dimorphic and organized by neonatal exposure to steroid hormones (Adler et al, 1999; Auger and Olesen, 2009; Bitran, 1993; Henley et al, 2011; Mora et al, 1996).…”

Epigenetic impacts of endocrine disruptors in the brain

“…In the rat brain, PCBs alter sexual differentiation of the AVPV and mPOA (Dickerson et al, 2011a; Dickerson et al, 2011b), reproductive senescence [aging; (Walker et al, 2013)], behavior [(Steinberg et al, 2007; Reilly et al, 2015; Bell et al, 2016b); reviewed in (Walker and Gore, 2007)] and cognition [(Widholm et al, 2001); Reviewed in (Schantz and Widholm, 2001; Boucher et al, 2009; Dzwilewski and Schantz, 2015)], outcomes that are influenced by changes in DNA methylation. Additionally, there is some evidence that perinatal exposure to PCBs altered expression of the methylation enzymes, DNMT1 and DNMT3a.…”