Abstract 617: Bisphenol A Inhibits GPR30-Mediated Dilation of Mesenteric Resistance Arteries

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sarah Lindsey ◽  
Melyssa Bratton ◽  
John A McLachlan
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Cardiovascular Effects ◽  
Mesenteric Arteries ◽  
The Novel ◽  
Resistance Arteries ◽  
Endocrine Disrupting Chemical ◽  
Downstream Signaling ◽  
Estrogenic Effects ◽  
Endocrine Disrupting

We previously showed that activation of the membrane estrogen receptor GPR30 decreases blood pressure in hypertensive ovariectomized mRen2.Lewis rats and acutely dilates mesenteric resistance arteries. These studies suggest that GPR30 plays a role in estrogen’s beneficial cardiovascular effects. Bisphenol A (BPA) is an endocrine-disrupting chemical found in most manufactured plastic products that also binds to GPR30 in the nanomolar range. Clinical studies show a significant correlation between elevated urinary BPA and increased diagnosis of cardiovascular diseases including hypertension. Therefore, we hypothesized that BPA may disrupt the vasodilatory effects mediated by the novel estrogen receptor GPR30. Second-order mesenteric arteries from 15 week-old Lewis females were denuded and mounted on a wire myograph. Arteries were preconstricted with 10 μM phenylephrine before assessing the response to increasing concentrations of the selective GPR30 agonist G-1 (0.001-3 μM). Pretreatment with 10 μM BPA significantly inhibited G-1-induced relaxation of denuded vessels (Figure, *P<0.01). In summary, BPA blocked the vasodilatory actions of G-1 in vascular smooth muscle, perhaps by competing for GPR30 and/or altering its downstream signaling. We conclude that human exposure to BPA may interfere with the protective estrogenic effects mediated by GPR30.

scholarly journals The different effects of endocrine-disrupting chemicals on estrogen receptor-mediated transcription through interaction with coactivator TRAP220 in uterine tissue

2003 ◽  
Vol 31 (3) ◽  
pp. 551-561 ◽  
Author(s):  
H Inoshita ◽  
H Masuyama ◽  
Y Hiramatsu
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine Function ◽  
Uterine Tissue ◽  
Present Evidence ◽  
Endocrine Disrupting Chemical ◽  
Positive Effects ◽  
Endocrine Disrupting

An endocrine-disrupting chemical (EDC) can alter endocrine functions through a variety of mechanisms, including nuclear receptor-mediated changes in protein synthesis, interference with membrane receptor binding, steroidogenesis or synthesis of other hormones. Although major chemicals have been shown to disrupt estrogenic actions mainly through their binding to estrogen receptor (ER) or androgen receptor, it is not clear how EDCs affect endocrine functions in vivo. We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated transcription through interaction with TRAP220. Moreover, bisphenol A had positive effects on the interaction between ER-beta and TRAP220 and on the expression of ER-beta and TRAP220 compared with phthalate and estradiol in uterine tIssue. These data suggested that some EDCs might alter endocrine function through the change of the receptor and coactivator levels in uterine tIssue and through the different effect on the interaction between ERs and coactivator TRAP220.

scholarly journals Micropillar/Microwell Chip Assessment for Detoxification of Bisphenol A with Korean Pear (Pyrus pyrifolia)

Micromachines ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 922
Author(s):  
Dong Lee ◽  
Moo-Yeal Lee ◽  
Sukkil Koh ◽  
Mihi Yang
Keyword(s):  
Bisphenol A ◽  
Liver Cells ◽  
Pyrus Pyrifolia ◽  
Endocrine Disrupting Chemical ◽  
Protein Levels ◽  
Ic50 Value ◽  
Endocrine Disrupting ◽  
Cultured Liver Cells ◽  
Ic50 Values ◽  
Hep3b Cells

A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA detoxification with Korean pear (Pyrus pyrifolia) extract, stimulators of ADH and ALDH, as well as arbutin, a reference compound in the pears, on the micropillar/microwell chip platform with human liver cells. Surprisingly, the toxicity of BPA was reduced in the presence of Korean pear extract, indicated by significantly increased IC50 values. The IC50 value of BPA with Korean pear extract tested against HepG2 cells was shifted from 151 to 451 μM, whereas those tested against Hep3B cells was shifted from 110 to 204 μM. Among the tested various concentrations, 1.25, 2.5, and 5 mg/mL of the extract significantly reduced BPA toxicity (Ps < 0.05). However, there was no such detoxification effects with arbutin. This result was supported by changes in protein levels of ADH in the liver cells.

Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

2014 ◽  
Vol 451 (4) ◽  
pp. 592-598 ◽  
Author(s):  
Yanzhen Liu ◽  
Chenfang Mei ◽  
Hao Liu ◽  
Hongsheng Wang ◽  
Guoqu Zeng ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Cytokine Expression ◽  
Endocrine Disrupting Chemical ◽  
Human Macrophages ◽  
Endocrine Disrupting

scholarly journals Epigenetic effects of Bisphenol A on granulosa cells of mouse follicles during in vitro culture: An experimental study

2021 ◽  
Author(s):  
Aylin Jamali Khaghani ◽  
Parisa Farrokh ◽  
Saeed Zavareh
Keyword(s):  
Bisphenol A ◽  
Granulosa Cells ◽  
Promoter Methylation ◽  
Inhibitory Effect ◽  
Promoter Regions ◽  
Endocrine Disrupting Chemical ◽  
Epigenetic Effects ◽  
Endocrine Disrupting ◽  
The Impact

Background: Bisphenol A (BPA), a synthetic endocrine-disrupting chemical, is a reproductive toxicant. Granulosa cells have significant roles in follicle development, and KIT ligand (KITL) and Anti-Müllerian hormone (AMH) are essential biomolecules produced by them during folliculogenesis. Objective: Due to the widespread use of BPA and its potential epigenetic effects, this study examined the impact of BPA on promoter methylation of amh and kitl genes in mouse granulosa cells. Materials and Methods: Preantral follicles were isolated from ovaries of immature mice and cultured for eight days. Then, follicles were treated with 50 and 100 μM of BPA, and 0.01% (v/v) ethanol for 24 and 72 hr. Growth and degeneration of follicles and antrum formation were analyzed. The granulosa cells were isolated mechanically, and their extracted DNA was treated with sodium bisulfite. The promoter regions of the amh and kitl were analyzed with PCR and sequencing. Results: BPA did not change follicle survival and antrum formation significantly (p = 0.41). However, the culture in the presence of 100 μM BPA had an inhibitory effect on growth. Before BPA treatment, the CpG of the kitl and amh promoters were unmethylated and partially methylated, respectively. While the percent of 5mC in the amh promoter reduced at 100 μM of BPA, it did not alter the kitl promoter methylation. Conclusion: BPA at higher concentrations has an inhibitory effect on follicle growth. Moreover, it seems that the epigenetic impact of BPA restricts to the demethylation of CpG sites. Key words: Bisphenol A, DNA methylation, Granulosa cells.

scholarly journals The Association between Bisphenol A, Steroid Hormones, and Selected MicroRNAs Levels in Seminal Plasma of Men with Infertility

2021 ◽  
Vol 10 (24) ◽  
pp. 5945
Author(s):  
Ewelina Palak ◽  
Weronika Lebiedzińska ◽  
Sławomir Anisimowicz ◽  
Maria Sztachelska ◽  
Piotr Pierzyński ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Seminal Plasma ◽  
Sperm Quality ◽  
Sperm Concentration ◽  
Circulating Mirnas ◽  
Endocrine Disrupting Chemical ◽  
Endocrine Disrupting ◽  
Healthy Control ◽  
Mirnas Expression ◽  
Semen Morphology

Bisphenol A (BPA), the most common endocrine-disrupting chemical, has been associated with male reproductive dysfunctions. Recently, it has been shown that BPA may also affect miRNAs expression. Herein, we aimed to evaluate the association of BPA levels with steroid hormone concentration and circulating miRNAs levels to investigate the potential direct effect of BPA on homeostasis in the testis environment. The level of BPA in the seminal plasma of azoospermic men was significantly higher compared to the healthy control. The concentrations of estradiol (E2) and androstenedione (A) were significantly decreased in the seminal plasma of azoospermic men compared to the normospermic men. The levels of miR-let-7a, miR-let-7b, and miR-let-7c were significantly up-regulated, and the level of miR-518f was significantly down-regulated in the seminal plasma of the azoospermic men compared to the healthy control. The level of BPA correlated negatively with sperm concentration and normal semen morphology. A significant positive correlation was found between BPA levels and miR-let-7a and miR-let-7c levels, whereas BPA negatively correlated with miR-518f levels. Our results suggest that BPA may negatively affect sperm quality. Moreover, BPA correlated with the miR-let-7a, miR-let-7c, and miR-518f levels in seminal plasma, which suggests that BPA may act directly in seminal plasma, affecting the testicular environment.

Bisphenol A Exposure Disrupts Enamel Formation via EZH2-Mediated H3K27me3

2021 ◽  
pp. 002203452199579
Author(s):  
H. Li ◽  
D. Cui ◽  
L. Zheng ◽  
Y. Zhou ◽  
L. Gan ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Progenitor Cells ◽  
Enamel Formation ◽  
Developmental Defects ◽  
Endocrine Disrupting Chemical ◽  
Complex Biological Process ◽  
Endocrine Disrupting ◽  
Repressive Histone Modification ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Excessive Proliferation

Enamel formation is a serial and complex biological process, during which related genes are expressed progressively in a spatiotemporal manner. This process is vulnerable to environmental cues, resulting in developmental defects of enamel (DDE). However, how environmental factors are biologically integrated during enamel formation is still poorly understood. Here, we investigated the mechanism of DDE elicited by a model endocrine-disrupting chemical, bisphenol A (BPA), in mouse incisors. We show that BPA exposure leads to DDE in mouse incisors, as well as excessive proliferation in dental epithelial stem/progenitor cells. Western blotting, chromatin immunoprecipitation sequencing, and immunofluorescence staining revealed that this effect was accompanied by upregulation of a repressive mark, H3K27me3, in the labial cervical loop of mouse incisors. Perturbation of H3K27me3 methyltransferase EZH2 repressed the level of H3K27me3 and partially attenuated the excessive proliferation in dental epithelial stem/progenitor cells and DDE induced by BPA exposure. Overall, our results demonstrate the essential role of repressive histone modification H3K27me3 in DDE elicited by exposure to an endocrine-disrupting chemical.

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