Co-expression network analysis identifies novel molecular pathways associated with cadmium and pyriproxyfen testicular toxicity in Gammarus fossarum

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.

Automated summary

Omics approaches are shedding light on the mechanisms of action of contaminants in environmentally relevant species, contributing to the development of molecular ecotoxicology. Co-expression network analysis proved effective in identifying key pathways and proteins associated with testicular toxicity in Gammarus fossarum exposed to endocrine disruptors. The study revealed distinct modules correlated with exposure to different contaminants, with specific functions identified for each module.