title: Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats.
abstract: Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life exposures to low doses of BPA exert long-lasting effects on animals' reproductive and brain physiology. However, little is known about the effects of BPA on the stress-response system. Given the interaction of sex and stress hormones, we examined the effect of a low perinatal BPA exposure on the function of the hypothalamic-pituitary-adrenal (HPA) axis at rest and upon application of acute stress. Throughout pregnancy and lactation rats received daily 40 μg BPA/kg body weight orally via cornflakes. We studied the effect of this low but chronic exposure to BPA in the male and female offspring at puberty. BPA exposure led to abnormal adrenal histology including reduced zona reticularis especially in male offspring, hyperplasia of zona fasciculata in both sexes, and increased adrenal weight in female offspring. BPA-treated females had increased basal corticosterone and reduced hypothalamic glucocorticoid receptors (GR) levels. Stressed BPA-exposed females exhibited anxiety-like behavioral coping, a less rigorous corticosterone response, and did not downregulate GR in the hypothalamus, compared with control females. BPA-exposed males exhibited a heightened corticosterone stress response compared with females; they also displayed increased pro-opiomelanocortin mRNA levels and retained the prestress levels of pituitary corticotropin-releasing hormone-receptor 1, compared with control males. We found that perinatal chronic exposure to a low dose of BPA perturbs the basal and stress-induced activity of the HPA axis in a sexually dimorphic manner at adolescence. Exposure to BPA might contribute to increased susceptibility to stress-related disorders in later life.
authors: Department of Basic Sciences and Oral Biology, School of Dentistry, National and Kapodistrian University of Athens, Thivon 2, 11527 Athens, Greece Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48, Vassileos Constantinou Avenue, 11635 Athens, Greece.
authors: Emily
authors: E
authors: Panagiotidou
authors: Sophia
authors: S
authors: Zerva
authors: Dimitra J
authors: DJ
authors: Mitsiou
authors: Michael N
authors: MN
authors: Alexis
authors: Efthymia
authors: E
authors: Kitraki
mesh_terms: D000818:Animals; D001007:Anxiety; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D003345:Corticosterone / Q000378:metabolism; D052244:Endocrine Disruptors / Q000009:adverse effects*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010636:Phenols / Q000009:adverse effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003345:Corticosterone; D052244:Endocrine Disruptors; D010636:Phenols; D011965:Receptors, Glucocorticoid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: HPA axis; adrenal cortex; bisphenol A; glucocorticoid receptor; rat