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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 ER? 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.

SUBMITTER: Patisaul HB

PROVIDER: S-EPMC3434201 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy.

Patisaul Heather B HB Sullivan Alana W AW Radford Meghan E ME Walker Deena M DM Adewale Heather B HB Winnik Bozena B Coughlin Janis L JL Buckley Brian B Gore Andrea C AC

PloS one 20120905 9

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 r ...[more]

PMID: 22957036

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Project description:BackgroundBisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.ObjectivesThe aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.MethodsPregnant F344 rats were exposed to BPA via their drinking water, corresponding to 0.5 ?g/kg BW/d (BPA0.5; n=21) or 50 ?g/kg?BW/d (BPA50; n=16), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (n=26). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.ResultsMales and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels (0.81±0.10 mmol/L compared with 0.57±0.03 mmol/L, females BPA50 p=0.04; 0.81±0.05 mmol/L compared with 0.61±0.04 mmol/L, males BPA0.5 p=0.005) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls (68.2±4.4 number of adipocytes/HPF compared with 55.9±1.5 number of adipocytes/HPF; p=0.03) and by 123% in BPA0.5 females compared with BPA50 animals (68.2±4.4 number of adipocytes/high power field (HPF) compared with 55.3±2.9 number of adipocytes/HPF; p=0.04). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals (69.9±5.1 number of adipocytes/HPF compared with 54.0±3.4 number of adipocytes/HPF; p=0.03). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.ConclusionsDevelopmental exposure to 0.5 ?g/kg?BW/d of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of 4 ?g/kg?BW/d and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at 0.5 ?g/kg?BW/d were compared with the offspring of unexposed controls. https://doi.org/10.1289/EHP505.

Dataset Information

Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy.

Publications

Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy.

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