title: Two-hit exposure to polychlorinated biphenyls at gestational and juvenile life stages: 2. Sex-specific neuromolecular effects in the brain.
abstract: 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.
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Bell
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Bethany G
authors.initials: BG
authors.lastname: Hart
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: andrea.gore@austin.utexas.edu.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Gore
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000235:genetics*; D011374:Progesterone / Q000097:blood; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D011078:Polychlorinated Biphenyls
keywords: Androgen receptor; Dopamine receptor; Endocrine-disrupting chemical; Estrogen receptor; Mu opioid receptor; Preoptic area