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Updated: Nov 9, 2025
A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of Caenorhabditis elegans
Published on: March 14, 2019
Co-expression network analysis identifies novel molecular pathways associated with cadmium and pyriproxyfen
Natacha Koenig1, Christine Almunia2, Aurore Bonnal-Conduzorgues1
1INRAE, UR RiverLy, Ecotoxicology Team. Centre de Lyon-Grenoble Auvergne Rhône-Alpes, 5 rue de la Doua CS 20244, 69625 Villeurbanne, France.
Abstract:
Omics approaches are continuously providing new clues on the mechanisms of action of contaminants in species of environmental relevance, contributing to the emergence of molecular ecotoxicology. Co-expression network approaches represent a suitable methodological framework for studying the rich content of omics datasets. This study aimed to find evidence of key pathways and proteins related to the testicular toxicity in the sentinel crustacean species Gammarus fossarum exposed to endocrine disruptors using a weighted protein co-expression network analysis. From a shotgun proteomics dataset of male gonads of G. fossarum organisms exposed to cadmium (Cd), pyriproxyfen (Pyr) and methoxyfenozide (Met) in laboratory conditions, four distinct modules were identified as significantly correlated to contaminants' exposure. Protein set enrichment analysis identified modules involved in cytoskeleton organization and oxidative stress response associated with the Cd exposure. The module associated with Pyr exposure was associated with endoplasmic reticulum stress (ER) response, and the module correlated with Met exposure was characterized by a significant proportion of amphipod-restricted proteins whose functions are still not characterized. Our results show that co-expression networks are efficient and adapted tools to identify new potential mode of actions from environmental sentinel species, such as G. fossarum, using a proteogenomic approach, even without an annotated genome.
Insights
Molecular ecotoxicology reveals how environmental contaminants impact species. Protein co-expression networks identified key pathways linked to testicular toxicity in Gammarus fossarum exposed to endocrine disruptors like cadmium.
Area of Science:
- Molecular ecotoxicology
- Proteomics
- Environmental science
Background:
- Omics approaches provide insights into contaminant mechanisms in environmental species.
- Co-expression network analysis is a powerful tool for interpreting omics data.
- Endocrine disruptors pose risks to aquatic ecosystems and wildlife.
Purpose of the Study:
- To investigate testicular toxicity mechanisms in Gammarus fossarum exposed to endocrine disruptors.
- To identify key proteins and pathways affected by cadmium, pyriproxyfen, and methoxyfenozide.
- To apply weighted protein co-expression network analysis to proteomics data.
Main Methods:
- Shotgun proteomics was performed on male gonads of Gammarus fossarum.
- Organisms were exposed to cadmium (Cd), pyriproxyfen (Pyr), and methoxyfenozide (Met) under laboratory conditions.
- Weighted protein co-expression network analysis and protein set enrichment analysis were employed.
Main Results:
- Four distinct co-expression modules significantly correlated with contaminant exposure were identified.
- Cadmium exposure was linked to cytoskeleton organization and oxidative stress response pathways.
- Pyriproxyfen exposure was associated with endoplasmic reticulum stress, and methoxyfenozide with uncharacterized amphipod-specific proteins.
Conclusions:
- Co-expression networks are effective for identifying contaminant modes of action in sentinel species.
- Proteogenomic approaches can reveal toxicity pathways even without a fully annotated genome.
- Gammarus fossarum serves as a valuable model for studying endocrine disruptor effects.
