Bisphenol A Disrupts Transcription and Decreases Viability in Aging Vascular Endothelial Cells

Significance Statement

Bisphenol A (BPA) is one of the greatest endocrine disruptor chemicals produced worldwide, employed in a wide variety of consumer products including food and drink containers. As a result human exposure to BPA through oral intake is considered generalized. Extensive research in human cell lines, particularly from sex steroids most responsive tissues, have shown that BPA exposure results in very distinct cellular responses, however although BPA is absorbed in the gut and enters blood circulation, its effects on cells from vascular or digestive systems are largely unknown. Here the exposure effects of two BPA concentrations (10 ng/ml and 1 mg/ml), relevant in the context of risk assessment were assessed in two distinct cell types; Human Umbilical Vein Endothelial Cells (HUVEC), an in vitro model for vascular cells, and the human cell line HT29, originated from a colon adenocarcinona, the most common type of gastrointestinal cancer. Quantitative real-time analysis based in the relative transcription of two LINE-1 sequences revealed a distinct response between HUVEC and HT29 cells being the BPA response lost with prolonged exposure in HT29 but increased in HUVEC. Additionally in aging HUVEC continuous exposure to BPA also results in disruption of global transcription associated with altered gene expression patterns of senescence related genes. Relevantly, in these conditions, BPA exposure resulted in severe cell viability decrease revealed by resazurin assay and cytological analysis (illustrated in figure). Several epidemiologic studies have established positive correlations between BPA exposure and vascular diseases and since HUVEC are an in vitro model for atherosclerosis pathogenesis our data supports the involvement of this environmental relevant chemical in the etiology of the disease.

Figure Legend: Continuous exposure of aging HUVEC (693 h from passage 12 to passage 19) to BPA resulted in a significant decrease in cell viability supported by the reduction in cell density. Aging HUVEC display a typical senescent phenotype characterized by augmented surface area, enlarged nuclear size (DNA DAPI staining in blue), stellate outlines, and microtubules enrichment (α-tubulin immunodetection in green). Bar = 50 μm.

Bisphenol A Disrupts Transcription and Decreases Viability in Aging Vascular Endothelial Cells







Journal reference

Ribeiro-Varandas E, Pereira HS, Monteiro S, Neves E, Brito L, Ferreira RB, Viegas W, Delgado M. Int J Mol Sci. 2014 Sep 9;15(9):15791-805. doi: 10.3390/ijms150915791.

Centro de Botânica Aplicada à Agricultura (CBAA), Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal.


Bisphenol A (BPA) is a widely utilized endocrine disruptor capable of mimicking endogenous hormones, employed in the manufacture of numerous consumer products, thereby interfering with physiological cellular functions. Recent research has shown that BPA alters epigenetic cellular mechanisms in mammals and may be correlated to enhanced cellular senescence. Here, the effects of BPA at 10 ng/mL and 1 µg/mL, concentrations found in human samples, were analyzed on HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells(HUVEC). Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) transcriptional analysis of the Long Interspersed Element-1 (LINE-1) retroelement showed that BPA induces global transcription deregulation in both cell lines, although with more pronounced effects in HUVEC cells. Whereas there was an increase in global transcription in HT29 exclusively after 24 h of exposure, this chemical had prolonged effects on HUVEC. Immunoblotting revealed that this was not accompanied by alterations in the overall content of H3K9me2 and H3K4me3 epigenetic marks. Importantly, cell viability assays and transcriptional analysis indicated that prolonged BPA exposure affects aging processes in senescent HUVEC. To our knowledge this is the first report that BPA interferes with senescence in primary vascular endothelial cells, therefore, suggesting its association to the etiology of age-related human pathologies, such as atherosclerosis.

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