Abstract
Bisphenol A (BPA) exposure has been suspected to be associated with deleterious effects on health including obesity and metabolically-linked diseases. Although bisphenols F (BPF) and S (BPS) are BPA structural analogs commonly used in many marketed products as a replacement for BPA, only sparse toxicological data are available yet. Our objective was to comprehensively characterize bisphenols gene targets in a human primary adipocyte model, in order to determine whether they may induce cellular dysfunction, using chronic exposure at two concentrations: a “low-dose” similar to the dose usually encountered in human biological fluids and a higher dose. Therefore, BPA, BPF and BPS have been added at 10 nM or 10 μM during the differentiation of human primary adipocytes from subcutaneous fat of three non-diabetic Caucasian female patients. Gene expression (mRNA/lncRNA) arrays and microRNA arrays, have been used to assess coding and non-coding RNA changes. We detected significantly deregulated mRNA/lncRNA and miRNA at low and high doses. Enrichment in “cancer” and “organismal injury and abnormalities” related pathways was found in response to the three products. Some long intergenic non-coding RNAs and small nucleolar RNAs were differentially expressed suggesting that bisphenols may also activate multiple cellular processes and epigenetic modifications. The analysis of upstream regulators of deregulated genes highlighted hormones or hormone-like chemicals suggesting that BPS and BPF can be suspected to interfere, just like BPA, with hormonal regulation and have to be considered as endocrine disruptors. All these results suggest that as BPA, its substitutes BPS and BPF should be used with the same restrictions.
Highlights
A variety of chemicals has been found to disrupt the endocrine system of animal models, and chemical exposure has been associated with adverse developmental and reproductive effects in fish and other wildlife [1]
Confluent pre-adipocytes were induced to differentiate with PBM-2 medium supplemented with insulin, dexamethasone, isobutylmethylxanthine and indomethacin for ten days according to the instructions of the manufacturer
All microarray data results were deposited on Gene Expression Omnibus website, under the accession number GSE98682 which includes both series of mRNA/Long non-coding RNAs (lncRNA) data (GPL16699) and miRNA data (GPL19730)
Summary
A variety of chemicals has been found to disrupt the endocrine system of animal models, and chemical exposure has been associated with adverse developmental and reproductive effects in fish and other wildlife [1]. Bisphenol A (BPA) exposure has been suspected to contribute to obesity and metabolic disorders [2]. The human population has a widespread exposure to BPA as it has been detected in 95% of the samples examined at concentrations !0.1 μg/L in urine [3],[4]. Associations were shown between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects [5]. High urinary BPA levels were found to be associated with obesity and type 2 diabetes (T2D) in several studies [6],[7],[8], but not all [9]
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