Common Gene Expression Patterns in Environmental Model Organisms Exposed to Engineered Nanomaterials: A Meta-Analysis

Abstract

The use of omics is gaining importance in the field of nanoecotoxicology; an increasing number of studies are aiming to investigate the effects and modes of action of engineered nanomaterials (ENMs) in this way. However, a systematic synthesis of the outcome of such studies regarding common responses and toxicity pathways is currently lacking. We developed an R-scripted computational pipeline to perform reanalysis and functional analysis of relevant transcriptomic data sets using a common approach, independent from the ENM type, and across different organisms, including Arabidopsis thaliana, Caenorhabditis elegans, and Danio rerio. Using the pipeline that can semiautomatically process data from different microarray technologies, we were able to determine the most common molecular mechanisms of nanotoxicity across extremely variable data sets. As expected, we found known mechanisms, such as interference with energy generation, oxidative stress, disruption of DNA synthesis, and activation of DNA-repair but also discovered that some less-described molecular responses to ENMs, such as DNA/RNA methylation, protein folding, and interference with neurological functions, are present across the different studies. Results were visualized in radar charts to assess toxicological response patterns allowing the comparison of different organisms and ENM types. This can be helpful to retrieve ENM-related hazard information and thus fill knowledge gaps in a comprehensive way in regard to the molecular underpinnings and mechanistic understanding of nanotoxicity.

Molecular Mechanisms of Nanomaterial-Bacterial Interactions Revealed by Omics—The Role of Nanomaterial Effect Level

“…These functional categories were indicative of mitochondrial-and DNA-related ENM effects and impaired signal transduction which are impacted in eukaryotic organisms upon cellular uptake of ENMs. Since these affected pathways were essential for the viability of the analyzed eukaryotic organisms, the omics findings expectedly confirmed the results of physiological assays (Burkard et al, 2020). An analysis of the prokaryotic pathway results conducted herein also indicated that the major affected pathways identified with omics techniques confirmed physiological assay findings: ENMs affect bacteria mainly via membrane damage, reactive oxygen species (ROS) generation and shedding of toxic metal ions that can contribute to excessive ROS and membrane damage.…”

“…The latter has been demonstrated with effective antibacterial surfaces such as vertically aligned graphene oxide nanosheets (Lu et al, 2017), or pronounced transcriptomic changes induced by ENMs assembled into micrometer-size agglomerates, which could not be internalized by bacteria due to size restrictions (Mortimer et al, 2020). Interestingly, the commonly affected KEGG pathways in bacteria across all ENMs and bacterial strains (Figure 1) included the same major cellular functions as were identified in multicellular organisms by Burkard et al (2020). Specifically, Burkard et al (2020) conducted a metaanalysis of transcriptomic data of three environmental model organisms, Arabidopsis thaliana, Caenorhabditis elegans, and Danio rerio, exposed to different ENMs, and revealed that common gene expression patterns across different organisms and ENMs included energy generation, general signaling, and DNA metabolism (Burkard et al, 2020).…”

Subtoxic dose of lithium cobalt oxide nanosheets impacts critical molecular pathways in trout gill epithelial cells

“…LCO NPs have been shown previously to induce oxidative stress and increase intracellular ROS production. 29,30 Oxidative stress and ROS are often attributed to mitochondrial damage, 52,57 which could also impact the metabolism related pathways identified in our study. In addition to the possible role of phosphate adsorption, hypoxia may impact metabolism as Table S1.…”

“…Engineered nanomaterials have been shown previously to disrupt the energy balance within cells, likely due to mitochondrial-related impacts. 51,52 Impacts to mitochondrial function may account for the upregulation of metabolism related pathways observed here. Furthermore, LCO NPs have been shown previously to adsorb phosphate in solution.…”

“…7 illustrates hypothesized connections and possible explanations for the observed regulated processes, which represent potential areas for future studies. The upregulation of metabolism related processes by both subtoxic and toxic NP doses suggests energy imbalance or depletion, possibly due to mitochondrial disfunction, 51,52 and cellular attempt to restore balance. We hypothesize this energy imbalance could result from NP-induced hypoxia, as suggested by the observed upregulation of pathways related to decreased oxygen levels and hypoxia by both the toxic and subtoxic doses at 24 and 48 hours.…”