Bisphenol A (BPA) is an environmental compounds is known to possess endocrine disruption potentials. Bisphenol A has epigenetic effects as deregulated expression of microRNAs; such epigenetic marks can induce up/down alterations in gene expression that may persist throughout a lifetime. Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development of offspring after BPA exposure during pregnancy are not yet widely studied. Therefore, the aim of this study was to gain a comprehensive understanding of microRNAs changes in the placenta transcriptome from pregnant women subjected to therapeutic abortion for fetal malformation and correlate the impact of gestational exposure to BPA on these developmental changes. We performed a comparative analysis of genome wide miRNA expression in placentas from pregnant women exposed to BPA using microarray technology to identify miRNAs which were aberrantly expressed in placentas from malformed fetuses. The expression changes of differential expressed miRNAs in the samples used for microarray were confirmed by qPCR . Beside, we applied various bioinformatics tools to predict the target genes of the identified miR-146a and explore their biological function and downstream pathways. We found that miR-146a was significant overexpressed and correlated significantly with BPA accumulation in the placenta from pregnant women living in a polluted area and undergoing therapeutic abortion due to fetal malformations. Beside, we applied various bioinformatics tools to predict the target genes of miR-146a and explore their biological function and downstream pathways. For the first time, we found, in humans, that miR-146a was significant over-expressed and correlated significantly with BPA accumulation in the placenta. Our results lead to the suggestion that miRNAs could be potential biomarkers to clarify the mechanisms of environmental diseases.

The main dietary flavonoid quercetin, is known to preserve the integrity of gastrointestinal barrier and to have anti-inflammatory, anti-cancer, anti-fibrotic, and other beneficial properties. Many of the biological effects of quercetin appear to be associated to the modulation of cell signaling pathways, rather than to its antioxidant activity. In spite of the large number of data available on the molecular and cellular mechanisms by which quercetin exerts its biological effects, including protection of intestinal barrier function, there is a lack of data about the role of this substance on the expression and/or the secretion of mucins released by intestinal goblet cells. Here we investigated the effects of quercetin on the secretion and the gene expression of the main intestinal gel-forming mucins, MUC2 and MUC5AC, and the signaling mechanisms underlined, in human intestinal goblet cell-like LS174T. We found that quercetin increases intracellular Ca²⁺ levels and induces MUC2 and MUC5AC secretion in a Ca²⁺-dependent manner. Quercetin also induces mRNA levels of both secretory mucins. Quercetin stimulation of LS174T cells increases phosphorylation levels of extracellular signal regulated kinase (ERK)1-2 and protein kinase C (PKC) α and the induction of MUC2 and MUC5AC secretion and mRNA relies on phospholipase C (PLC), PKC, and ERK1-2 signaling pathways since the PLC inhibitor U73122, the PKC inhibitor bisindolylmaleimide (BIM) and the ERK1-2 pathway inhibitor PD98059, all revert the stimulatory effects of quercetin. We also demonstrated that the induction of mucin gene expression by quercetin is not limited to goblet cells. Indeed, quercetin induces mRNA levels of MUC2 and MUC5AC via PKCα/ERK1-2 pathway also in the human intestinal epithelial Caco-2 cells. These data highlight a novel mechanism thereby quercetin, regulating the secretory function of intestinal goblet cells and mucin levels in enterocytes may exert its protective effects on intestinal mucosal barrier.