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Antibiotics are widely consumed in the intensive mariculture industry. A better understanding of the effect of antibiotics on intergenerational antibiotic resistance in organisms is urgent since intergenerational transmission is crucial for the spread of antibiotic resistance genes (ARGs) in the environment. Herein, marine medaka (Oryzias melastigma) chronically exposed to low doses of sulfamethazine (SMZ) hormetically affected the progeny, characterized by increased richness and diversity of fecal microbiota and intestinal barrier-related gene up-regulation. Progeny immunity was modulated and caused by genetic factors due to the absence of significant SMZ accumulation in F1 embryos. In addition, some of the top genera in the progeny were positively correlated with immune diseases, while the expression of some immune-related genes, such as TNFα, IL1R2, and TLR3 changed significantly. This further indicated that the host selection caused by changes in progeny immunity was probably the primary determinant of progeny intestinal microbial colonization. Metagenomic analysis revealed that Proteobacteria represented the primary carriers of ARGs, while parental SMZ exposure facilitated the distribution and enrichment of multiple ARGs involved in the antibiotic inactivation in the progeny by promoting the diversity of Gammaproteobacteria and Bacteroidetes, further illustrating that antibiotic selection pressure persisted even if the offspring were not exposed. Therefore, SMZ induced hormesis in the progeny at the expense of increasing antibiotic resistance. Collectively, these findings provide a comprehensive overview of the intergenerational effect of antibiotics and serve as a reminder that the ARG transmission induced by the intergenerational impact of antibiotics on organisms should not be ignored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

So far, few data are available on the reproductive toxicological assessment of β-diketone antibiotics (DKAs), a class of ubiquitous pseudo-persistent pollutant, in zebrafish (Danio rerio). Herein, we reported the reproductive effects of DKAs by means of transcriptome analysis (F1-zebrafish), changes in a series of reproductive indices (F0-zebrafish) and histopathological observations. A total of 1170, 983 and 1399 genes were found to be differentially expressed when compared control vs. 6.25mg/L, control vs. 12.5mg/L and 6.25 vs. 12.5mg/L DKA-exposure treatments, respectively. Among three comparison groups, 670, 569 and 821 genes were respectively assigned for GO analyses based on matches with sequences of known functions. In 149 KEGG-noted metabolic pathways, the preferential one was the MAPK (mitogen-activated protein kinase) signaling pathway, followed by oxidative phosphorylation, neuroactive ligand-receptor interaction and so on. By qPCR verification, 6 genes (c6ast4, igfbp1b, mrpl42, tnnc2, emc4 and ddit4) showed consistent gene expression with those identified by transcriptome sequencing. Due to DKA-exposure, the concentrations of plasma estradiol and testosterone, and the gonado-somatic index were significantly dose-dependently declined. Also, DKA-exposure led to declining in zebrafish reproductive capacity, reflecting in fertilization, hatchability and egg production. Histopathological observations demonstrated that zebrafish ovary and testis suffered serious damage after DKA-exposure. The 4-oxo-TEMP signals increased obviously with increasing DKA-exposed concentrations, implying disruption of balance between generation and clearance of 1 O 2 . In summary, DKAs not only produce reproductive toxicological effects on F0-zebrafish, but also result in adverse consequences for growth and development of F1-zebrafish., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Transcriptome analysis is important for interpreting the functional elements of the genome and revealing the molecular constituents of cells and tissues. Herein, differentially transcribed genes were identified by deep sequencing after zebrafish (Danio rerio) were exposed to β-diketone antibiotics (DKAs); 23,129 and 23,550 mapped genes were detected in control and treatment groups, a total of 3238 genes were differentially expressed between control and treatment groups. Of these genes, 328 genes (213 up- and 115 down-regulation) had significant differential expression (p < 0.05) and an expression ratio (control/treatment) of >2 or <0.5. Additionally, we performed Gene Ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and found 266 genes in the treatment group with annotation terms linked to the GO category. A total of 77 differentially expressed transcriptional genes were associated with 132 predicted KEGG metabolic pathways. Serious liver tissue damage was reflected and consistent with the differences in genetic classification and function from the transcriptome analysis. These results enhance our understanding of zebrafish developmental processes under exposure to DKA stress. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1357-1371, 2016., (© 2015 Wiley Periodicals, Inc.)

Fluoroquinolones (FQs) and tetracyclines (TCs), the two β-diketone antibiotics (DKAs), are two frequently detected pollutants in the environment; however, little data are available on their combined toxicity to zebrafish (Danio rerio). This study reports that toxicologic effects of combined DKA (FQs-TCs) exposure on zebrafish were comparable with or slightly less than those of TCs alone, showing that TCs played a major toxicologic role in the mixtures. The effects of FQs, TCs, and DKAs on malformation rates of zebrafish were dose dependent, with EC50 values of 481.3, 16.4, and 135.1 mg/L, respectively. According to the combined effects of DKAs on zebrafish hatching, mortality, and malformation rates, the interaction between FQs and TCs was shown to be antagonistic based on three assessment methods: Toxic Unit, Additional Index, and Mixture Toxic Index. The 1.56 mg/L TC and 9.38 mg/L DKA treatments resulted in higher zebrafish basal swimming rate compared with the control group at 120 hours postfertilization (hpf). in both light and light-to-dark photoperiod experiments. Under conditions of no obvious abnormality in cardiac development, the heart beats were decreased significantly because of DKA exposure, such as decreasing by ∼20% at 150 mg/L DKAs. Transmission electron microscopy observation of myocytes from DKA-exposed hearts displayed prominent interruptions and myofibrillar disorganization of the normal parallel alignment of thick and thin filaments, and partial edematous and dissolved membranes of cell nuclear tissues. At 90 mg/L DKAs, the transcriptional levels of the acta1a, myl7, and gle1b genes, related to heart development and skeletal muscle formation, were significantly changed. This is consistent with the swimming behavior and histopathologic results obtained by transmission electron microscopy. In summary, the toxicity of the combined DKAs to zebrafish was comparable with or less than that of TCs alone and had the ability to impair individual behaviors that are of great importance in the assessment of their ecologic fitness. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 736-750, 2016., (© 2014 Wiley Periodicals, Inc.)