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

College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
Institute of Precision Diagnostics and Translational Medicine, UHCW NHS Trust, Coventry CV4 7AL, UK
Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
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;
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.

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.

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.

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