title: Sex differences in the adult HPA axis and affective behaviors are altered by perinatal exposure to a low dose of bisphenol A.
abstract: Bisphenol A (BPA), an estrogen-mimicking endocrine disrupter, when administered perinatally can affect affective behaviors in adult rodents, however the underlying mechanisms remain largely unclear. Postnatal day (PND) 80 vehicle-injected control female rats showed more obvious depression- and anxiety-like behaviors than males, indicative of sexually dimorphic affective behaviors. When female breeders were subcutaneously injected with BPA (2µg/kg) from gestation day 10 to lactation day 7, sex difference of affective behaviors was impaired in their offspring (PND80 BPA-rats), as results that female BPA-rats showed a visible "antianxiety-like" behavior, and male BPA-rats increased depression-like behavior compared to vehicle-injected controls. Notably, basal levels of serum corticosterone and adrenocorticotropin (ACTH), and corticotropin-releasing hormone mRNA were increased in male BPA-rats, but not in female BPA-rats, in comparison with vehicle-injected controls. Following mild-stressor the elevation of corticosterone or ACTH levels was higher in male BPA-rats, whereas it was lower in female BPA-rats than vehicle-injected controls. In comparison with vehicle-injected controls, the level of glucocorticoid receptor (GR) mRNA in hippocampus or hypothalamic paraventricular nucleus was increased in female BPA-rats, while decreased in male BPA-rats. In addition, the levels of hippocampal mineralocorticoid receptor (MR) mRNA, neuronal nitric oxide synthase (nNOS) and phospho-cAMP response element binding protein (p-CREB) were increased in female BPA-rats, but were decreased in male BPA-rats. Furthermore, the testosterone level was reduced in male BPA-rats. The results indicate that the perinatal exposure to BPA through altering the GR and MR expression disrupts the GR-mediated feedback of hypothalamic-pituitary-adrenal (HPA) axis and MR-induced nNOS-CREB signaling, which alters sex difference in affective behaviors.
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing 210029, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing 210029, China.
authors.forename: Yinyang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China. Electronic address: zhou-rong@hotmail.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000339:Affect / Q000187:drug effects*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003623:Dark Adaptation / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D013550:Swimming / Q000523:psychology; D013739:Testosterone / Q000097:blood; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D050882:CREB-Binding Protein; D004968:Estrogens, Non-Steroidal; D019001:Nitric Oxide Synthase; D010636:Phenols; D013739:Testosterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Affective behaviors; Bisphenol A; Glucocorticoid receptor; Hypothalamic–pituitary–adrenal axis; Mineralocorticoid receptor