4.5 Article

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

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 420, Issue C, Pages 125-137

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2015.11.024

Keywords

Endocrine-disrupting chemical; Preoptic area; Dopamine receptor; Mu opioid receptor; Androgen receptor; Estrogen receptor

Funding

  1. NIH [RO1 ES020662, RO1 ES023254, T32 ES07247, F32 ES023291]

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Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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