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 mg 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.

Environmental Health Factors and Sexually Dimorphic Differences in Behavioral Disruptions

“…It will be essential to disentangle direct effects of BPA on brain development from indirect effects of BPA that may be mediated by altered parental behavior. BPA reduces hypothalamic GR expression [160], which might exaggerate glucocorticoid responses to stress. It has also been suggested that BPA can directly bind and activate GR [77], which would be another avenue by which BPA can affect later social and environmental stressors [161].…”

Estrogenic activity of isoflavonoids from the stem bark of the tropical tree Amphimas pterocarpoides , a source of traditional medicines

“…Confluent cells were cultured for 2 days in the presence of 2% FBS and 5 mg/mL insulin and induced to terminally differentiate by a 3-day treatment with 5 mg/mL insulin, 100 nM dexamethasone and 5 mg/mL prolactin (PRL) in the absence or presence of estradiol (10 nM), test compounds or vehicle ( 0.2% DMSO) with or w/o ICI182,780 (1 mM). Extraction of total RNA, reverse transcription (RT) and quantitative PCR (qPCR) analysis of casein mRNA expression were performed as previously described [24]. Casein mRNA levels were normalized to the respective levels of glycerol-3-phosphate dehydrogenase (GAPDH).…”

This can't be stressed enough: The contribution of select environmental toxicants to disruption of the stress circuitry and response

“…Behavioral data from animal studies suggesting BPA-induced alterations in the stress response are corroborated by concurrent increases in plasma levels of CORT, and in some instances increases in ACTH and CRH in the offspring who have been developmentally exposed to BPA compared with control animals (116, 119, 121, 124). In some instances these elevations in CORT were also accompanied by changes in the expression of the GR and MR in various regions involved in the stress response.…”