Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

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 st...

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Bibliographic Details
Published in:	Journal of endocrinology Vol. 220; no. 3; pp. 207 - 218
Main Authors:	Panagiotidou, Emily, Zerva, Sophia, Mitsiou, Dimitra J, Alexis, Michael N, Kitraki, Efthymia
Format:	Journal Article
Language:	English
Published:	England Bioscientifica Ltd 01-03-2014
Subjects:	Animals Anxiety Benzhydryl Compounds - adverse effects Corticosterone - metabolism Endocrine Disruptors - adverse effects Female Hypothalamo-Hypophyseal System - drug effects Hypothalamo-Hypophyseal System - growth & development Hypothalamo-Hypophyseal System - metabolism Male Organ Size Phenols - adverse effects Pituitary-Adrenal System - drug effects Pituitary-Adrenal System - growth & development Pituitary-Adrenal System - metabolism Pregnancy Prenatal Exposure Delayed Effects - genetics Prenatal Exposure Delayed Effects - metabolism Prenatal Exposure Delayed Effects - physiopathology Prenatal Exposure Delayed Effects - psychology Rats Rats, Wistar Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - metabolism Stress, Physiological glucocorticoid receptor bisphenol A HPA axis rat adrenal cortex
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Summary:	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.
ISSN:	0022-0795 1479-6805
DOI:	10.1530/JOE-13-0416