Environmentally Relevant Sulfamethoxazole Induces Developmental Toxicity in Embryo-Larva of Marine Medaka (Oryzias melastigma)

Sulfamethoxazole (SMX), a commonly used sulfonamide antibiotic, poses a threat to aquatic life due to its widespread presence in the environment. This study aims to investigate the specific effects of SMX on the development of marine medaka (Oryzias melastigma) embryos and larvae. Marine medaka embryos were exposed to SMX at concentrations of 0 (solvent control group, SC group), 1 μg/L (low concentration group, L group), 60 μg/L (middle concentration group, M group), and 1000 μg/L (high concentration group, H group). The results indicated that SMX exposure significantly accelerated the heart rate of embryos (p < 0.0001) and shortened the hatching time while also causing anomalies such as reduced pigmentation, smaller eye size, spinal curvature, and yolk sac edema. SMX also led to a decrease in the total length of the larvae. The M group and the H group exhibited a significant increase (p < 0.05) in lipid accumulation in the visceral mass of the larvae. In the L group and the M group, there was a significant increase (p < 0.0001) in the swimming distance of the larvae. At the molecular level, SMX exposure affected the transcript levels of the genes involved in the cardiovascular system (ahrra, arnt2, atp2a1, and cacan1da), antioxidant and inflammatory systems (cat, cox-1, gpx, pparα, pparβ, and pparγ), nervous system (gap43, gfap, α-tubulin), intestinal barrier function (claudin-1), detoxification enzymes (ugt2c1-like), and lipid metabolism (rxraa) in the embryos to larval stage. The microbiome analysis showed that at the phylum level, exposure to SMX resulted in an increase in the abundance of Proteobacteria. Additionally, the abundance of Actinobacteriota significantly increased in the L group (p < 0.05). At the genus level, the abundance of Bifidobacterium significantly increased in the L group (p < 0.05), while the abundance of Vibrio significantly increased in the H group (p < 0.05). The alpha diversity analysis revealed a significant decrease in the Chao1 index in the L and H groups, indicating a reduction in microbial richness. The beta diversity analysis showed differences in the microbial communities of marine medaka larvae among different SMX exposure groups. This study elucidates the negative impacts of SMX on the development of marine medaka embryos and larvae and their microbial composition, providing a scientific basis for assessing the risks of SMX in marine ecosystems.