| With their excellent bacteriostatic efficacy,antibiotics have been applyed broadly in the treatment of human diseases,livelihood and aquaculture.Due to the high demand for antibiotics and improper disposal of expired antibiotics,a large amount of antibiotics were released into the natural environment through various ways.Serious antibiotics pollution may pose potential risks to organisms and ecosystems.Sulfonamide antibiotics including sulfamethazine(SM2)were common antibiotic pollutants owning to their broad-spectrum antimicrobial effect and cheapness.Ocean is a main sink of different pollutants and antibiotics have a high emission in the coastal areas.Therefore,it is necessary to develop the study of antibiotic in marine ecotoxicology.Marine medaka(Oryzias melastigma)is an euryhaline fish which has a small size,short generation time,high reprodutive rate and strong adaptability.It is considered as a promising marine model organism and is more frequently applied in ecotoxicological study now.Hence,this study employed marine medaka as experienmental animals.Combining transcriptome sequencing analysis,real-time fluorescence quantitative PCR assay,morphological index statistics and other methods,we studied the hepatotoxicity and reproductive toxicity of SM2 and explored the intrirnsic toxicity mechanism.The results of study were listed as follows:Transcriptome analysis of hepatotoxicity showed that SM2 acute exposure caused stressed to marine medaka and affected the expression and regulation of related genes and pathways.The response patterns of male and female fish to SM2 treatment are different in a gender specific manner.For male fish,lipid metabolism and redox reaction are more active,major GO enrichment were related to energy metabolism and the significant enrichment pathway was PPAR signaling pathway.For female fish,glycometabolism was more active.And diabetes-related pathways were significantly enriched in high dose SM2 treatment.At the same time,there were some cancer-related pathways,such as mTOR signaling pathway,enriched in both low and high dose treatments.Some up-regulated differential expressed genes were significantly enriched in Ovarian Steroidogenesis pathway in high dose SM2 treatment.It may imply high dose SM2 can affect the reproduction of marine medaka.Besides,the study also found that high dose SM2 treatment can lead to the significant enrichment of autoimmune thyroid disease pathway in both male and female fish.Thyroid related genes Om03190g00280 appeared a notable down-regulated expression.This gene may be a suitable biomarker for detecting SM2 toxicity.As for reproductive toxicity study,according to the result of real-time fluorescence quantitative PCR assay and statistical data of morphological indexs,we speculated that SM2 had disrupting effects on the reproduction of marine medaka and the power of this effect was strengthened with the increasement of SM2 dose.Fish would initiate the regulation mechanism of reproductive compensation when subjected to SM2 stress.They improved survival rate of offspring by increasing spawning frequency(higher spawning rate),but reducing the number of eggs(lower egg producion,egg envelope formation related genes were down-regulated)and ensured the probablity of fertilization.Moreover,the higher dose of SM2 could induced the physiological response of fish more quickly because of its stronger stress effect.When the dose of SM2 did not exceed the threshold,the adaptability of the fish would be enhanced with the prolongation of SM2 exposure time.In addition,SM2 still interfered with cardiac development of embryos that their parents were under SM2 pollution.This toxicity may have a transgenerational effect.Our study analyzed the preliminay intrinsic toxicity of SM2 to marine medaka and discussed the relevant toxicity mechanism.This study can provide some references for exploring toxicity of SM2 in other aquatic organisms and assessing the ecological risk of SM2 abuse. |
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