Impact of copper nanoparticles (CuNPs) on gonadal development in zebrafish larvae and melatonin therapeutic...

Copper nanoparticles (CuNPs), owing to their high specific surface area and reactivity, are extensively applied across various fields while concurrently posing certain hazards to aquatic organisms. This study comprehensively investigated the detrimental effects of CuNPs on the reproductive system of zebrafish and emphasized the examination of the potential therapeutic role of melatonin. The research found that CuNPs interfere with zebrafish gonadal development through oxidative damage, endocrine disruption (upregulated estradiol, E₂; downregulated testosterone, T), and suppression of reproduction-related genes, consequently causing impaired germ cell development and even organismal mortality. Through transcriptomic research, we discovered that CuNPs induce gonadal oxidative stress (Oxidative phosphorylation pathway) and endoplasmic reticulum stress (Protein processing in endoplasmic reticulum pathway), downregulate zgc:153,993 to activate the mitochondrial apoptosis pathway, and inhibit the hsp70l-MAPK/ERK feedback loop to amplify damage; the organism compensatorily upregulated cyp2x12 to enhance detoxification function and upregulated dync1i1/dync1li2 to activate the Phagosome pathway to clear aberrant apoptotic products. Melatonin, by antagonizing ROS and repairing stress-induced damage, modulated the expression of most key gonadal development genes to restore homeostasis. Simultaneously, it transcriptionally upregulated ribosome biogenesis gene (si:dkey-103j14.5) and lysosomal pathway gene (si:ch211-122f10.4) to alleviate nucleic acid oxidation damage and clear damaged substrates. Finally, by upregulating got2a to activate the aspartate metabolism pathway, it achieved multi-target therapeutic intervention against gonadal injury under CuNPs exposure. Our study reveals the physiological and molecular mechanisms underlying the reproductive toxicity of CuNPs; melatonin, as an endogenous protective agent, shows promise in mitigating the ecotoxicological effects of CuNPs.