PMID- 32028606 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 9 IP - 2 DP - 2020 Feb 3 TI - Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. LID - 10.3390/jcm9020405 [doi] LID - 405 AB - 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. FAU - de Aguiar Greca, Sophie-Christine AU - de Aguiar Greca SC AD - College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK. FAU - Kyrou, Ioannis AU - Kyrou I AD - Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK. AD - Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK. AD - Institute of Precision Diagnostics and Translational Medicine, UHCW NHS Trust, Coventry CV4 7AL, UK. AD - Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. FAU - Pink, Ryan AU - Pink R AD - Dept of Bio. & Med. Sci., Oxford Brookes University, Oxford OX3 0BP, UK. FAU - Randeva, Harpal AU - Randeva H AD - Institute of Precision Diagnostics and Translational Medicine, UHCW NHS Trust, Coventry CV4 7AL, UK. AD - Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. FAU - Grammatopoulos, Dimitris AU - Grammatopoulos D AD - Institute of Precision Diagnostics and Translational Medicine, UHCW NHS Trust, Coventry CV4 7AL, UK. AD - Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. FAU - Silva, Elisabete AU - Silva E AD - College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK. FAU - Karteris, Emmanouil AU - Karteris E AD - College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK. LA - eng PT - Journal Article DEP - 20200203 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC7074564 OTO - NOTNLM OT - BPA OT - endocrine-disrupting chemicals OT - microarray OT - placenta COIS- The authors declare no conflict of interest. EDAT- 2020/02/08 06:00 MHDA- 2020/02/08 06:01 PMCR- 2020/02/03 CRDT- 2020/02/08 06:00 PHST- 2019/12/26 00:00 [received] PHST- 2020/01/22 00:00 [revised] PHST- 2020/01/23 00:00 [accepted] PHST- 2020/02/08 06:00 [entrez] PHST- 2020/02/08 06:00 [pubmed] PHST- 2020/02/08 06:01 [medline] PHST- 2020/02/03 00:00 [pmc-release] AID - jcm9020405 [pii] AID - jcm-09-00405 [pii] AID - 10.3390/jcm9020405 [doi] PST - epublish SO - J Clin Med. 2020 Feb 3;9(2):405. doi: 10.3390/jcm9020405.