Anxiogenic Effects of Developmental Bisphenol A Exposure Are Associated with Gene Expression Changes in the Juvenile Rat Amygdala and Mitigated by Soy

Abstract

Early life exposure to Bisphenol A (BPA), a component of polycarbonate plastics and epoxy resins, alters sociosexual behavior in numerous species including humans. The present study focused on the ontogeny of these behavioral effects beginning in adolescence and assessed the underlying molecular changes in the amygdala. We also explored the mitigating potential of a soy-rich diet on these endpoints. Wistar rats were exposed to BPA via drinking water (1 mg/L) from gestation through puberty, and reared on a soy-based or soy-free diet. A group exposed to ethinyl estradiol (50 µg/L) and a soy-free diet was used as a positive estrogenic control. Animals were tested as juveniles or adults for anxiety-like and exploratory behavior. Assessment of serum BPA and genistein (GEN), a soy phytoestrogen, confirmed that internal dose was within a human-relevant range. BPA induced anxiogenic behavior in juveniles and loss of sexual dimorphisms in adult exploratory behavior, but only in the animals reared on the soy-free diet. Expression analysis revealed a suite of genes, including a subset known to mediate sociosexual behavior, associated with BPA-induced juvenile anxiety. Notably, expression of estrogen receptor beta (Esr2) and two melanocortin receptors (Mc3r, Mc4r) were downregulated. Collectively, these results show that behavioral impacts of BPA can manifest during adolescence, but wane in adulthood, and may be mitigated by diet. These data also reveal that, because ERβ and melanocortin receptors are crucial to their function, oxytocin/vasopressin signaling pathways, which have previously been linked to human affective disorders, may underlie these behavioral outcomes.

Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring

“…Thus, this study showed that perinatal exposure of GEN did not affect locomotor activity or emotionality. With regard to emotionality, a previous report suggested that GEN from soy-based diets could mitigate anxiogenic-induced effects of developmental exposure to Bisphenol A (BPA) [33]. Although there was little effect of GEN itself on anxiety in our study, it could be that GEN has the ability to relieve anxiety from an already anxiogenic condition.…”

Influence of housing variables on the development of stress-sensitive behaviors in the rat

“…Patisaul et al recently reported that developmental exposure to the ED Bisphenol A (BPA) results in an anxiogenic phenotype in adulthood in rats. However, this anxiogenic phenotype was mitigated if rats were provided with a soy-based diet, demonstrating a strong interaction between EDs in the environment and soy in the diet [57].…”

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

“…For each experiment, all Wistar rats were obtained from Charles River (Raleigh, North Carolina) and/or bred in house as indicated in humidity-and-temperature controlled rooms, each with a 12 h:12 h light, dark cycle at 25 C and 45-60% average humidity at the Biological Resource Facility at NCSU. As in our prior studies (Patisaul et al, 2012(Patisaul et al, , 2009, and in accordance with recommended practices for endocrine-disrupting chemicals (EDC) research (Hunt et al, 2009;Li et al, 2008;Richter et al, 2007), all animals were housed in conditions specifically designed to minimize unintended EDC exposure including use of glass water bottles, soy-free diet, woodchip bedding, and thoroughly washed polysulfone caging. Individual authentic standards of EH-TBB,…”