Genome–wide microRNA expression profiling in placentas from pregnant women exposed to BPA

Abstract

BackgroundBisphenol 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.MethodsWe 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.ResultsWe 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.ConclusionsFor 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.

Impact of preimplantational oral low‐dose estradiol‐17β exposure on the endometrium: The role of miRNA

“…Many studies have demonstrated effects of an exposure to EDCs during embryo development directly on mothers and offspring as well as long‐term effects in the latter (Amstislavsky et al, , ; Geisert et al, ; Gore et al, ; Ma et al, ; Ross et al, ). Little is known about EDCs affecting miRNAs (Felice et al, ; Meunier et al, ; Nothnick & Healy, ; Veiga‐Lopez et al, ). A former study has demonstrated direct in utero effects of bisphenol A altering fetal ovarian miRNA expression in sheep (Veiga‐Lopez et al, ).…”

“…In addition, the mechanisms of miRNAs altering mRNA expression are well studied and it has been predicted that miRNAs regulate about 50% of all mammalian protein‐coding genes (Krol, Loedige, & Filipowicz, ; Roberts, ; Zhou, Hu, & Lai, ). Still, there is especially little knowledge about effects on miRNA expression through EDCs during the early stages of development (Felice et al, ; Meunier et al, ; Nothnick & Healy, ; Veiga‐Lopez, Luense, Christenson, & Padmanabhan, ).…”

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

“…BPA exposure induces DNA methylation and histone protein modifications in the brain and other organs [72; 114; 115; 116; 117; 118; 119; 120; 121]. The expression of miRNAs in the placenta, liver, and likely other organs, including the brain, can also be influenced by BPA [122; 123; 124; 125]. Bisphenols may also induce neuroendocrine disruptive effects by targeting the gut-microbiome-brain axis [126; 127; 128; 129; 130].…”

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

“…Notably, these effects were seen at 100 nM to 50 µM concentrations of BBP with the decreased dimethylation effect occurring in the concentration range of 100 nM to 10 µM. Decreased trimethylation of histone H3K9(me3) and increased expression of miR-146a have also been shown in multiple cell types following exposure to BPA but have not yet been directly shown in MSCs (123, 146, 147). …”