van Lingen, H. J. | bioRxiv Science

bioRxiv2025

Gene expression profile dynamics of earthworms exposed to ZnO and ZnO:Mn nanomaterials

Zinc oxide containing nanomaterials may elicit toxic responses in environmental organisms such as earthworms. Although toxic responses in earthworms have been reported, few studies have attempted to understand the molecular mode of action dynamics explaining the observed toxicity at a transcriptional level. This study investigates the time-dependent gene expression response in earthworms exposed to ZnO nanomaterials and ZnO:Mn multicomponent nanomaterials. Earthworms were exposed to ZnO or ZnO:Mn for 7 days and to ZnO:Mn or MnCl2 for 14 days. Strong differential gene expression responses were observed after 4 days of exposure to ZnO nanomaterials and after 2 days of exposure to ZnO:Mn. Moderate differential gene expression responses were observed after 14 days of exposure to ZnO:Mn and MnCl2. Gene ontology (GO) enrichment analysis revealed that differentially expressed genes in earthworms exposed to ZnO were associated with terms such as actin, (striated) muscle cells, contractile fiber, myofibril, sarcomere and supramolecular cellular components. In addition, genes that were upregulated after 2 days of exposure to ZnO:Mn were linked to GO terms including cilium, microtubule, cell projection, axoneme and sperm flagellum cellular components. Downregulated genes were enriched to GO terms related to ribosomes, mitochondria, translation, peptide processes, respiration and oxidative phosphorylation. Finally, for earthworms exposed to ZnO:Mn and MnCl2 for 14 days, only a limited number of differentially expressed genes were involved in GO terms related to diverse biological implications. In summary, exposing earthworms to the ZnO and ZnO:Mn nanomaterials elicited a transient response in differential gene expression related to muscle biology and energy metabolism and translation that had largely disappeared by day 14 from the start of the exposure.

systems biology↗

bioRxiv2024

Predicting uptake and elimination kinetics of chemicals in invertebrates: a technicalnote on residual variance modeling

Toxicokinetic models for predicting contents of nanomaterials and other toxic chemicals are often fitted without evaluation of the residual variance structure. The aim of the present study was to evaluate various residual variance structures, assuming either homoscedasticity or heteroscedasticity, when fitting non-linear toxicokinetic one-compartment models for predicting uptake, bioaccumulation and elimination of chemicals in invertebrate organisms. Data describing the exposure of several aquatic and terrestrial invertebrates to specific metal nanomaterials and other chemicals were available from real experiments for evaluating the residual variance functions for toxicokinetic models. As proof of concept, datasets of truly homoscedastic and heteroscedastic nature were simulated. Depending the dataset, applying models with different residuals variance assumption largely affected the residual plots and the error margins of parameters or the predicted content of a chemical. Consequently, selecting the most accurate residual variance functions for toxicokinetic modeling, either homoscedastic or heteroscedastic, improves the prediction of chemical contents in invertebrate organisms and the estimation of the associated uptake and elimination rates. HighlightsO_LIResidual plots indicate if an accurate model was fitted to the toxicological data C_LIO_LIChoice of residual variance function affects the error margins of predicted chemicals C_LIO_LISelecting proper residual variance models may prevent false positives and negatives C_LI

pharmacology and toxicology↗