Transgenerational effects of microplastics on Nrf2 signaling, GH/IGF, and HPI axis in marine medaka Oryzias melastigma under different salinities

Little information is available on the toxicity of microplastics (MPs) under different salinities in aquatic or-ganisms. Consequently, the effects of larvae exposure to 180 mu g/L MPs with 5.0 mu m diameter on growth, anti-oxidant capacity and stress response were investigated in exposed F1 larvae and unexposed F2 larvae in marine medaka Oryzias melastigma at 5 %o and 25 %o salinities. Poor growth performance of F1 and F2 larvae and F1 adult fish was merely found under high salinity, as well as changes in the growth hormone/insulin-like growth factor-I (GH/IGF). Although malondialdehyde (MDA) content and antioxidant capacity remained constant in F1 larvae under high salinity, MPs increased MDA content and reduced antioxidant capacity in F2 larvae. Contrarily, MDA and antioxidant capacity increased in F1 and F2 larvae under low salinity. The mRNA expression levels of genes in the NF-E2-related factor 2 (Nrf2) pathway were dysregulated. Cortisol levels in the whole body increased in F1 larvae and recovered to the control level under low salinity while cortisol levels declined in F1 larvae and increased in F2 larvae under high salinity, which was related to the transcriptional regulation of the hypothalamus-pituitary-interrenal (HPI) axis genes. To summary, the present study determined the toxic effects of MPs on growth, antioxidant capacity, and stress response by disturbing Nrf2, HPI, and GH/IGF signaling in exposed larvae and unexposed offspring of marine medaka in a salinity-dependent manner. For the first time, our results highlight the interference effects of salinity on MPs toxicity in fish.