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

Abstract

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.

Publication DOI: https://doi.org/10.3390/jcm9020405
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Publication ISSN: 2077-0383
Last Modified: 04 Mar 2024 08:38
Date Deposited: 23 Mar 2020 12:44
Full Text Link:
Related URLs: https://www.mdp ... 77-0383/9/2/405 (Publisher URL)
PURE Output Type: Article
Published Date: 2020-02-03
Accepted Date: 2020-01-23
Authors: de Aguiar Greca, Sophie-Christine
Kyrou, Ioannis (ORCID Profile 0000-0002-6997-3439)
Pink, Ryan
Randeva, Harpal
Grammatopoulos, Dimitris
Silva, Elisabete
Karteris, Emmanouil

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