Effects and mechanisms of lipidomic and development alterations in ire-1 mutant Caenorhabditis elegans under extremely low-frequency electromagnetic field exposure

This study assessed the effects and underlying mechanisms of 50 Hz extremely low-frequency electromagnetic field (ELF-EMF) on lipid metabolism and development in ire-1 mutant Caenorhabditis elegans. Lipidomic profiling revealed 87 lipids with significant alterations following ELF-EMF exposure, and Biological Pathway Analysis (BioPAN) revealed activated conversion of phosphatidylserine to phosphatidylethanolamine, enhanced dihydroceramide synthesis, and suppressed lysophosphatidylinositol to phosphatidylinositol in ire-1 worms. Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Enzyme-Linked Immunosorbent Assay (ELISA) methods were utilized for further verification of lipidic alterations in ire-1 worms following ELF-EMF exposure. Significant elevation of Ca²⁺ and slight enhancement of hsp-4::GFP were observed, suggesting that endoplasmic reticulum (ER) stress may be activated independently of IRE-1, with concurrent upregulation of Activating Transcription Factor (ATF) gene expressions. Developmental inhibition was observed, characterized by 22.3% reduction in body length and 28.7% decrease in brood size. The adaptive antioxidant responses were detected as evidenced by 11.0% increased superoxide dismutase activity, 18.6% enhanced total antioxidant capacity, and 53.4% decreased malondialdehyde content. In summary, 50 Hz ELF-EMF exposure can disrupt both lipid metabolism and developmental processes in ire-1 worms, inducing striking calcium homeostasis dysregulation, ER stress, and oxidative stress responses. Unfolded protein responses were suggested to be activated independently of IRE-1, possibly involving the PERK/ATF4 pathway. ELF-EMF may act as an oxidative stress-like factor to activate ER stress and adaptive antioxidant responses in ire-1 worms.