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

2013 ◽  
Vol 220 (3) ◽  
pp. 207-218 ◽  
Author(s):  
Emily Panagiotidou ◽  
Sophia Zerva ◽  
Dimitra J Mitsiou ◽  
Michael N Alexis ◽  
Efthymia Kitraki
Keyword(s):  
Stress Response ◽  
Bisphenol A ◽  
Hpa Axis ◽  
Chronic Exposure ◽  
Glucocorticoid Receptors ◽  
Low Dose ◽  
Female Offspring ◽  
Zona Fasciculata ◽  
Mrna Levels ◽  
Brain Physiology

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.

Perinatal oral exposure to low doses of bisphenol A, S or F impairs gut barrier and immune functions in female offspring mice

2019 ◽  
Author(s):  
Yann Malaisé ◽  
Corinne Lencina ◽  
Christel Cartier ◽  
Maïwenn Olier ◽  
Sandrine Ménard ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Immune Responses ◽  
Bisphenol A ◽  
Low Dose ◽  
Intestinal Barrier ◽  
Female Offspring ◽  
Oral Exposure ◽  
Gut Barrier ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract Background Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 mg/kg body weight (BW)/day (d)) on gut barrier and immune system in female offspring mice at adulthood (Post Natal Day PND70). Methods Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at PostNatal Day (PND) 21. Gut barrier function and the humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels. Results In female offspring, perinatal oral BP exposure led to adverse effects on intestinal barrier and immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5µg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG, revealing a defect of gut barrier. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of gut barrier functions and cellular immune responses, provoking an intestinal and systemic Th1/Th17 inflammation. Conclusion These findings provide, for the first time, a comparative study of long-time consequences of BPA, S and F perinatal exposure by oral route in offspring mice. This work warms that it is mandatory to consider immune markers and dose in risk assessment associated to new BPA’s alternatives. Keywords: Bisphenol A, Bisphenol S, Bisphenol F, Immune responses, Perinatal exposure, Intestine, Th1/Th17, immunoglobulin, cytokines

Sex differences in the adult HPA axis and affective behaviors are altered by perinatal exposure to a low dose of bisphenol A

2014 ◽  
Vol 1571 ◽  
pp. 12-24 ◽  
Author(s):  
Fang Chen ◽  
Libin Zhou ◽  
Yinyang Bai ◽  
Rong Zhou ◽  
Ling Chen
Keyword(s):  
Sex Differences ◽  
Bisphenol A ◽  
Hpa Axis ◽  
Low Dose ◽  
Perinatal Exposure ◽  
Affective Behaviors

scholarly journals Repeated maternal glucocorticoid administration and the developing liver in fetal sheep

2002 ◽  
Vol 175 (2) ◽  
pp. 535-543 ◽  
Author(s):  
DM Sloboda ◽  
JP Newnham ◽  
Keyword(s):  
Hpa Axis ◽  
Plasma Glucose ◽  
Glucocorticoid Receptors ◽  
Fetal Liver ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Insulin Levels ◽  
Protein Levels ◽  
Cord Plasma ◽  
Glucocorticoid Administration

Prenatal glucocorticoid exposure has been associated with a reduction in birth weight and postnatal alterations in glucose homeostasis and hypothalamic-pituitary-adrenal (HPA) axis function. The mechanisms underlying these responses are unknown, although changes in fetal hepatic development may play an important role. The fetal liver produces key regulators of fuel metabolism and of the developing HPA axis that are altered by glucocorticoids. The local availability of glucocorticoids is regulated, in part, by corticosteroid-binding protein (CBG), glucocorticoid receptors (GR) and by the enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD), but the effects of maternal glucocorticoid administration on the expression of these genes in the fetal liver are unknown. 11betaHSD1 is the predominant form of this enzyme present in the liver and is responsible for the conversion of cortisone to cortisol. To determine if prenatal glucocorticoid exposure alters fetal hepatic regulation of CBG, 11betaHSD1 and GRs, we treated pregnant ewes with betamethasone (0.5 mg/kg) intramuscularly at 104, 111 and 118 days of gestation (term 150 days). Animals were killed at 125 or 146 days of gestation. Maternal betamethasone administration did not alter mean cord plasma glucose but significantly decreased cord plasma insulin levels (P<0.05) at 125 days of gestation. At 146 days of gestation, cord plasma glucose levels were significantly increased without alterations in insulin levels following maternal betamethasone treatment (P<0.05). Maternal betamethasone administration resulted in a significant increase in fetal hepatic 11betaHSD1 mRNA and protein levels at 125 days of gestation (P<0.05). CBG mRNA levels were significantly elevated over control at 125 days although levels of CBG protein were not significantly different. GR protein levels were not statistically different at either 125 or 146 days of gestation following glucocorticoid administration. These data suggest that prenatal betamethasone exposure in the ovine fetus results in alterations in cord glucose and insulin levels as well as alterations in hepatic 11betaHSD1 mRNA and protein expression. These changes in 11betaHSD1 increase the potential to generate local cortisol from circulating cortisone. We speculate that this could affect expression of glucocorticoid-dependent hepatic enzymes involved with the regulation of glucose production and HPA responsiveness.

scholarly journals TheKampoMedicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shoko Shimizu ◽  
Takashi Tanaka ◽  
Takashi Takeda ◽  
Masaya Tohyama ◽  
Shingo Miyata
Keyword(s):  
Hpa Axis ◽  
Stress Responses ◽  
Glucocorticoid Receptors ◽  
Psychological Symptoms ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Stress Exposure ◽  
Protein Levels ◽  
Hpa Axis Activity ◽  
The Brain

It is well known that glucocorticoid receptor (GR) signaling regulates the hypothalamic-pituitary-adrenal (HPA) axis, and GR expression level is associated with HPA axis activity. Recent studies revealed that microRNA- (miR-) 18 and/or 124a are candidate negative regulators of GR in the brain. TheKampomedicine Yokukansan (YKS) can affect psychological symptoms such as depression and anxiety that are associated with stress responses. In this study, we evaluated the effect of YKS on miR-18 and 124a and GR levels in mice exposed to stress. We found that YKS pretreatment normalized elevated plasma corticosterone levels in stress-exposed mice. In addition, GR mRNA levels were downregulated in the brain following stress exposure. While miR-124a expression levels were not altered in the hypothalamus of stress-exposed mice, miR-18 levels decreased in the hypothalamus of YKS-pretreated mice after stress exposure. Finally, GR protein levels in the paraventricular nucleus (PVN) of the hypothalamus after stress exposure recovered in YKS-pretreated mice. Collectively, these data suggest that YKS normalizes GR protein levels by regulating miR-18 expression in the hypothalamus, thus normalizing HPA axis activity following stress exposure.

scholarly journals Low-dose Bisphenol-A regulates inflammatory cytokines through GPR30 in mammary adipose cells

2019 ◽  
Vol 63 (4) ◽  
pp. 273-283 ◽  
Author(s):  
Ilaria Cimmino ◽  
Francesco Oriente ◽  
Vittoria D’Esposito ◽  
Domenico Liguoro ◽  
Pasquale Liguoro ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Inflammatory Cytokines ◽  
Fatty Acid Synthase ◽  
Low Dose ◽  
Stromal Vascular Fraction ◽  
Mrna Levels ◽  
Environmental Chemical ◽  
Dramatic Rise ◽  
Signaling Activation ◽  
Inflammatory Molecules

The dramatic rise in obesity and metabolic syndrome can be related, at least in part, to environmental chemical factors such as Bisphenol-A (BPA). In this study, we aimed to understand the effects of low-dose Bisphenol-A on the human mature adipocytes and stromal vascular fraction (SVF) cells, obtained from subcutaneous mammary adipose tissue of overweight female patients, undergoing surgical mammary reduction. 24 and/or 48-h exposure to BPA 0.1 nM elicited significant increase of the inflammatory molecules interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemo-attractant protein 1α (MCP1α) and induced G protein-coupled estrogen receptor 30 (GPR30) levels more than two-fold both in mature adipocytes and SVF cells. These effects were similar to that obtained in the presence of GPR30-specific agonist G1 (100 nM) and were reverted by G15 (1 µM), a GPR30-selective antagonist. As a result of BPA-GPR30 signaling activation, fatty acid synthase (FAS) and leptin mRNA levels were significantly higher upon BPA exposure (P < 0.05) in mature adipocytes, with an opposite effect on adiponectin (ADIPOQ). In addition, an increase in SVF cell proliferation and ERK1/2 phosphorylation, was observed, compared to untreated cells. G15 reverted all of these effects. Interestingly, the action of BPA on SVF cell growth was mimicked by IL-8 treatment and was reverted by incubation with anti-IL8 antibodies. All these data suggest that BPA at 0.1 nM, a ten times lower concentration than environmental exposure, increases the expression of pro-inflammatory cytokines via GPR30 both in mature mammary adipocytes and in SVF cells with a possible involvement of IL-8.

scholarly journals Chronic exposure to low dose of bisphenol A impacts on the first round of spermatogenesis via SIRT1 modulation

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Rosanna Chianese ◽  
Andrea Viggiano ◽  
Konrad Urbanek ◽  
Donato Cappetta ◽  
Jacopo Troisi ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Chronic Exposure ◽  
Low Dose

scholarly journals Chronic Corticosterone Exposure Increases Expression and Decreases Deoxyribonucleic Acid Methylation of Fkbp5 in Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4332-4343 ◽  
Author(s):  
Richard S. Lee ◽  
Kellie L. K. Tamashiro ◽  
Xiaoju Yang ◽  
Ryan H. Purcell ◽  
Amelia Harvey ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Chronic Exposure ◽  
Psychiatric Symptoms ◽  
Neuronal Cell ◽  
Fold Increase ◽  
Epigenetic Mechanism ◽  
Mrna Levels ◽  
Elevated Plus Maze Test ◽  
Plus Maze ◽  
Single Cell Type

There is evidence for hypercortisolemia playing a role in the generation of psychiatric symptoms and for epigenetic variation within hypothalamic-pituitary-adrenal (HPA) axis genes mediating behavioral changes. We tested the hypothesis that expression changes would be induced in Fkbp5 and other HPA axis genes by chronic exposure to corticosterone and that these changes would occur through the epigenetic mechanism of loss or gain of DNA methylation (DNAm). We administered corticosterone (CORT) to C57BL/6J mice via their drinking water for 4 wk and tested for behavioral and physiological changes and changes in gene expression levels using RNA extracted from hippocampus, hypothalamus, and blood for the following HPA genes: Fkbp5, Nr3c1, Hsp90, Crh, and Crhr1. The CORT mice exhibited anxiety-like behavior in the elevated plus maze test. Chronic exposure to CORT also caused a significant decrease in the hippocampal and blood mRNA levels of Nr3c1 and a decrease in Hsp90 in blood and caused an increase in Fkbp5 for all tissues. Differences were seen in Fkbp5 methylation in hippocampus and hypothalamus. To isolate a single-cell type, we followed up with an HT-22 mouse hippocampal neuronal cell line exposed to CORT. After 7 d, we observed a 2.4-fold increase in Fkbp5 expression and a decrease in DNAm. In the CORT-treated mice, we also observed changes in blood DNAm in Fkbp5. Our results suggest DNAm plays a role in mediating effects of glucocorticoid exposure on Fkbp5 function, with potential consequences for behavior.

scholarly journals The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression

Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2353-2361 ◽  
Author(s):  
Dharmendra Sharma ◽  
Robert J. Handa ◽  
Rosalie M. Uht
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Hpa Axis ◽  
Steroid Receptor ◽  
Camp Response Element Binding ◽  
Mrna Levels ◽  
Camp Response Element ◽  
Response Element ◽  
Steroid Receptor Coactivator ◽  
Element Binding Protein

The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression.

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