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Article

Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation

1
College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
2
Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK
3
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
4
Institute of Precision Diagnostics and Translational Medicine, UHCW NHS Trust, Coventry CV4 7AL, UK
5
Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
6
Dept of Bio. & Med. Sci., Oxford Brookes University, Oxford OX3 0BP, UK
*
Authors to whom correspondence should be addressed.
The last two authors should be considered joint last due to equal contributions in the manuscript.
J. Clin. Med. 2020, 9(2), 405; https://doi.org/10.3390/jcm9020405
Received: 26 December 2019 / Revised: 22 January 2020 / Accepted: 23 January 2020 / Published: 3 February 2020
Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding the complete spectrum of BPA-induced effects on the human placenta. As such, the present study examined the effects of physiologically relevant doses of BPA in vitro. Methods: qRT-PCR, Western blotting, immunofluorescence, ELISA, microarray analyses, and bioinformatics have been employed to study the effects of BPA using nonsyncytialised (non-ST) and syncytialised (ST) BeWo cells. Results: Treatment with 3 nM BPA led to an increase in cell number and altered the phosphorylation status of p38, an effect mediated primarily via the membrane-bound estrogen receptor (GPR30). Nonbiased microarray analysis identified 1195 and 477 genes that were differentially regulated in non-ST BeWo cells, whereas in ST BeWo cells, 309 and 158 genes had altered expression when treated with 3 and 10 nM, respectively. Enriched pathway analyses in non-ST BeWo identified a leptin and insulin overlap (3 nM), methylation pathways (10 nM), and differentiation of white and brown adipocytes (common). In the ST model, most significantly enriched were the nuclear factor erythroid 2-related factor 2 (NRF2) pathway (3 nM) and mir-124 predicted interactions with cell cycle and differentiation (10 nM). Conclusion: Collectively, our data offer a new insight regarding BPA effects at the placental level, and provide a potential link with metabolic changes that can have an impact on the developing fetus. View Full-Text
Keywords: endocrine-disrupting chemicals; BPA; placenta; microarray endocrine-disrupting chemicals; BPA; placenta; microarray
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MDPI and ACS Style

de Aguiar Greca, S.-C.; Kyrou, I.; Pink, R.; Randeva, H.; Grammatopoulos, D.; Silva, E.; Karteris, E. Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. J. Clin. Med. 2020, 9, 405. https://doi.org/10.3390/jcm9020405

AMA Style

de Aguiar Greca S-C, Kyrou I, Pink R, Randeva H, Grammatopoulos D, Silva E, Karteris E. Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. Journal of Clinical Medicine. 2020; 9(2):405. https://doi.org/10.3390/jcm9020405

Chicago/Turabian Style

de Aguiar Greca, Sophie-Christine, Ioannis Kyrou, Ryan Pink, Harpal Randeva, Dimitris Grammatopoulos, Elisabete Silva, and Emmanouil Karteris. 2020. "Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation" Journal of Clinical Medicine 9, no. 2: 405. https://doi.org/10.3390/jcm9020405

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