Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.09.15.751754

EFFECTS OF SUBCHRONIC EXPOSURE TO POLYSTYRENE NANOPLASTICS ON THE MOUSE INTESTINE

Gregory, M.·Dufresne, J.·Da Cunha de Medeiros, P.·Yim, S.·Moinard, P.·Gagne, F.·Cyr, D.
View original source ↗Export metadata ↓

Abstract

Nanoplastics (NPs) are being used increasingly in cosmetics, personal care products, foods, automotive products, and cleaning products, as well as being by-products of some industrial processes. The aim of this study was to examine the effects of a sub-chronic exposure of NPs on various biological systems, using mice as a model. Adult male mice were administered 500 nm polystyrene (PS) NPs at 0.15 mg/day and 1.5 mg/day, to mimic subchronic exposure to NPs. Control mice were gavaged in the same manner but with sterile water instead of NPs. The mice were weighed weekly and treated daily for 60 days. The mice were then euthanized, and multiple tissues were retrieved and fixed or frozen for subsequent analyses. The intestines were rinsed and divided into pieces of the three regions: duodenum, jejunum, and ileum. Hematoxylin and eosin (H&E) staining was performed to evaluate histopathology, and RNA-Seq was conducted on tissues from all three regions. H&E staining revealed few effects on the duodenum, but increasingly pronounced disruption and epithelial alterations in the jejunum and ileum, respectively. RNA-Seq analysis of controls compared to the high-dose (HD; 1.5 mg/day) group supported these observations. The number of differentially expressed genes (DEGs) was low (19) in the duodenum, higher in the jejunum (114 DEGs), and significantly greater in the ileum (4982 DEGs). Genes associated with immune response, ion transport, and junctional proteins were among the groups of genes most differentially expressed. These results demonstrate the potentially harmful effects of PS NPs on the intestinal system of mice.

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Gregory, M., Dufresne, J., Da Cunha de Medeiros, P., Yim, S., Moinard, P., Gagne, F., Cyr, D.. 2026-09-21. EFFECTS OF SUBCHRONIC EXPOSURE TO POLYSTYRENE NANOPLASTICS ON THE MOUSE INTESTINE. https://doi.org/10.64898/2026.09.15.751754

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A metastable GαS/β-arrestin complex sustains endosomal PTH1R signaling

G protein-coupled receptors (GPCRs) initiate cellular signaling by activating heterotrimeric G proteins at the plasma membrane and are silenced when beta-arrestin binds the phosphorylated receptor, preventing G protein binding. However, many receptors continue to generate cAMP after internalization, even while barr is bound, a paradox that lacked a molecular mechanism in live cells. A direct barrestin1-Gas interface in the PTH1R-barr1-Gas complex has recently been defined structurally, but whether the complex operates in endosomes, and how it behaves there, has not been established. Using intact cells, we examine the assembly at three spatial resolutions. Confocal imaging with a nanobody selective for nucleotide-free Gas places activated Gas, barr, and agonist-occupied PTH1R on the same endosomes. Single-molecule localization microscopy, with illumination modes that separate the plasma membrane from the endosomal membrane in single cells, shows that the agonist recruits Gas and barr at both membranes. FRET, however, reveals a specific interaction only on endosomes, where a Gas inhibitor restricted to that compartment abolishes the sustained cAMP phase without affecting receptor internalization. Weighted-ensemble-enhanced molecular simulations show that the complex is metastable, releasing Gas through a large rigid-body rotation away from barr while barr itself tightens its interactions with the receptor. These findings provide a molecular basis for endosomal Gs/cAMP signaling and open a new avenue for drug development targeting this pathway.

pharmacology and toxicology↗
bioRxiv2026

Advancing AOPs for genotoxicity through quantifying KERs linking DNA alkylation to increase in mutations and chromosome aberrations

Quantitative Adverse Outcome Pathways (qAOPs) help translate mechanistic knowledge into quantitative toxicity predictions; however, their development is constrained by the limited availability and heterogeneity of quantitative data. Here, we investigated the feasibility of developing a qAOP for genotoxicity by modeling quantitative relationships linking DNA alkylation to increased mutations and structural chromosome aberrations through intermediate biological key events (KEs). We compiled and harmonized published concentration-response data from human lymphoblastoid TK6 cells exposed to ethyl methanesulfonate, methyl methanesulfonate, or N-ethyl-N-nitrosourea, covering eight genotoxicity assays representing five KEs with well-established dependencies. We evaluated sources of variability, compared points of departure (PoDs), and quantified relationships between successive events using response-response modeling. Substantial between-study variability could to a limited extent be explained through differences in experimental design while batch effects for individual studies and researchers were substantial. PoD estimates that were calculated from combined results of independent studies with similar experimental design, were often uncertain due to insufficient concentration-response characterization or conflicting results between studies. Nevertheless, response-response modeling suggested a threshold effect for certain key-event relationships (KERs). Specifically, DNA adducts seemed to be triggered at lower concentrations of alkylating agents compared to the subsequent KEs of DNA strand breaks and chromosome aberrations. Furthermore, these fitted response-response models can be used for prediction of downstream KEs from earlier ones. The general approach we developed for BMC analysis followed by response-response modeling is applicable to other AOPs as well. These findings highlight both the feasibility and limitations of using existing data for qAOP development.

pharmacology and toxicology↗
bioRxiv2026

Denaturation-sensitive BRET probes enable intracellular thermal shift measurements across diverse protein targets and biomolecular complexes

Thermal shift assays have revolutionized drug discovery, but can be limited in sensitivity and scalability. Combining the unique attributes of differential scanning fluorimetry (DSF) and cellular thermal shift (CETSA), we report the methodological framework for the bioluminescence resonance energy transfer shift assay (BRETSA). BRETSA utilizes denaturation sensitive BRET probes, in combination with luciferase-tagged target proteins, to track and longitudinally record thermal shift in living cells. Denaturation profiles were successfully measured for over 500 globular proteins, spanning 24 target families in diverse cellular compartments. Among these, target engagement was confirmed for over 200 proteins; including validated drug targets as well as understudied members of the kinase subfamily. Leveraging orthosteric, allosteric, and covalent ligands in potency studies, this method offers improved sensitivity and scalability compared to other thermal shift methods. We extend the utility of BRETSA to interrogate target engagement at biomolecular complexes and query cooperative binding for molecular glues and emerging tricomplex drug modalities.

pharmacology and toxicology↗