scholarly journals Oral exposure of low-dose bisphenol A promotes proliferation of dorsolateral prostate and induces epithelial–mesenchymal transition in aged rats

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Dong-Yan Huang ◽  
Cheng-Cheng Zheng ◽  
Qi Pan ◽  
Shuang-Shuang Wu ◽  
Xin Su ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Epithelial Mesenchymal Transition ◽  
Oral Exposure ◽  
Aged Rats ◽  
Mesenchymal Transition

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

Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats

2019 ◽  
Vol 35 (10) ◽  
pp. 647-659 ◽  
Author(s):  
Shuangshuang Wu ◽  
Dongyan Huang ◽  
Xin Su ◽  
Han Yan ◽  
Jianhui Wu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Synergetic Effect ◽  
Oral Exposure ◽  
Signal Pathways ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Egfr Expression ◽  
Endocrine Hormone ◽  
Prostate Diseases

Prostate is sensitive to endocrine hormone level, and the synergetic effect of estrogen and androgen is critical in prostate growth. The change of signal pathways caused by the imbalance of estrogen and androgen might function in the occurrence of prostate diseases. As a well-known endocrine disruptor compound, bisphenol A (BPA) can disturb the normal function of endocrine hormone and affect prostate development. This study aims to investigate effects of BPA on the dorsolateral prostate (DLP) and the related gene expression of the tissue in adult Sprague- Dawley (SD) rats and to explore the mechanism for the effect of low-dose BPA on DLP hyperplasia. Three-month-old male SD rats were treated with BPA (10.0, 30.0, or 90.0 µg (kg.day)−1, gavage) or vehicle (gavage) for 4 weeks. BPA significantly increased the DLP weight, the DLP organ coefficient, and the prostate epithelium height ( p < 0.01) of rats dose-dependently. Microarray analysis and quantitative real-time polymerase chain reaction showed that BPA significantly upregulated the transcriptional levels of some genes, including pituitary tumor transforming gene 1, epidermal growth factor, Sh3kbp1, and Pcna. Furthermore, the expression of PCNA ( p < 0.01), androgen receptor ( p < 0.01), and EGF receptor (EGFR) ( p < 0.001) in DLP was increased significantly by BPA treatment, and the expression of estrogen receptor alpha was also upregulated. The findings evidenced that low-dose BPA could induce DLP hyperplasia in adult rats, and the upregulated EGF/EGFR pathway that was responsive to estrogen and androgen might play an essential role in the DLP hyperplasia induced by low-dose BPA.

scholarly journals Oral exposure to low dose bisphenol A aggravates allergic airway inflammation in mice

2019 ◽  
Vol 6 ◽  
pp. 1253-1262 ◽  
Author(s):  
Rie Yanagisawa ◽  
Eiko Koike ◽  
Tin-Tin Win-Shwe ◽  
Hirohisa Takano
Keyword(s):  
Bisphenol A ◽  
Airway Inflammation ◽  
Low Dose ◽  
Allergic Airway Inflammation ◽  
Oral Exposure

scholarly journals Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression

2020 ◽  
Vol 21 (18) ◽  
pp. 6829
Author(s):  
Mong-Lien Wang ◽  
Yi-Fan Hsu ◽  
Chih-Hsuan Liu ◽  
Ya-Ling Kuo ◽  
Yi-Chen Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Acetylcholine Receptor ◽  
Cell Lines ◽  
Nicotinic Acetylcholine Receptor ◽  
Low Dose ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Specimen ◽  
Nicotinic Acetylcholine ◽  
Mesenchymal Transition

Nicotine in tobacco smoke is considered carcinogenic in several malignancies including lung cancer. The high incidence of lung adenocarcinoma (LAC) in non-smokers, however, remains unexplained. Although LAC has long been less associated with smoking behavior based on previous epidemiological correlation studies, the effect of environmental smoke contributing to low-dose nicotine exposure in non-smoking population could be underestimated. Here we provide experimental evidence of how low-dose nicotine promotes LAC growth in vitro and in vivo. Screening of nicotinic acetylcholine receptor subunits in lung cancer cell lines demonstrated a particularly high expression level of nicotinic acetylcholine receptor subunit α5 (α 5-nAChR) in LAC cell lines. Clinical specimen analysis revealed up-regulation of α 5-nAChR in LAC tumor tissues compared to non-tumor counterparts. In LAC cell lines α 5-nAChR interacts with epidermal growth factor receptor (EGFR), positively regulates EGFR pathway, enhances the expression of epithelial-mesenchymal transition markers, and is essential for low-dose nicotine-induced EGFR phosphorylation. Functionally, low-dose nicotine requires α 5-nAChR to enhance cell migration, invasion, and proliferation. Knockdown of α 5-nAChR inhibits the xenograft tumor growth of LAC. Clinical analysis indicated that high level of tumor α 5-nAChR is correlated with poor survival rates of LAC patients, particularly in those expressing wild-type EGFR. Our data identified α 5-nAChR as an essential mediator for low-dose nicotine-dependent LAC progression possibly through signaling crosstalk with EGFR, supporting the involvement of environmental smoke in tumor progression in LAC patients.

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