Bis(2-ethylhexyl)-tetrabromophthalate Poses a Higher Exposure Risk and Induces Gender-Specific Metabolic Disruptions in Zebrafish Liver.

Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.

Multi- and Transgenerational Developmental Impairments Are Induced by Decabromodiphenyl Ethane (DBDPE) in Zebrafish Larvae.

A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant; hence, the knowledge of its long-term toxic effects and underlying mechanism would be critical for further health risk assessment. In the present study, the multi- and transgenerational toxicity of DBDPE was investigated in zebrafish upon a life cycle exposure at environmentally relevant concentrations. The significantly increased malformation rate and declined survival rate specifically occurred in unexposed F2 larvae suggested transgenerational development toxicity by DBDPE. The changing profiles revealed by transcriptome and DNA methylome confirmed an increased susceptibility in F2 larvae and figured out potential disruptions of glycolipid metabolism, mitochondrial energy metabolism, and neurodevelopment. The changes of biochemical indicators such as ATP production confirmed a disturbance in the energy metabolism, whereas the alterations of neurotransmitter contents and light-dark stimulated behavior provided further evidence for multi- and transgenerational neurotoxicity in zebrafish. Our findings also highlighted the necessity for considering the long-term impacts when evaluating the health of wild animals as well as human beings by emerging pollutants.

Evaluation and Mechanistic Study of Transgenerational Neurotoxicity in Zebrafish upon Life Cycle Exposure to Decabromodiphenyl Ethane (DBDPE).

The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant in the environment, which may evoke imperceptible effects in humans or wild animals. Hence in this study, zebrafish embryos were exposed to DBDPE (0, 0.1, 1, and 10 nM) until sexual maturity (F0), and F1 and F2 generations were cultured without further exposure to study the multi- and transgenerational toxicity and underlying mechanism. The growth showed sex-different changing profiles across three generations, and the social behavior confirmed transgenerational neurotoxicity in adult zebrafish upon life cycle exposure to DBDPE. Furthermore, maternal transfer of DBDPE was not detected, whereas parental transfer of neurotransmitters to zygotes was specifically disturbed in F1 and F2 offspring. A lack of changes in the F1 generation and opposite changing trends in the F0 and F2 generations were observed in a series of indicators for DNA damage, DNA methylation, and gene transcription. Taken together, life cycle exposure to DBDPE at environmentally relevant concentrations could induce transgenerational neurotoxicity in zebrafish. Our findings also highlighted potential impacts on wild gregarious fish, which would face higher risks from predators.

Transcriptome reveals overview of Ca2+ dose-dependent metabolism disorders in zebrafish larvae after Cd2+ exposure.

Cadmium (Cd), a ubiquitous environmental hazardous heavy metal, poses a significant threat to the health of aquatic organisms, including teleosts. Although the toxic profile of Cd is well recognized, little is known regarding the overall view of toxic responses to varying aquatic environmental parameters (e.g., water hardness) at an individual level. Herein, differences in water hardness were partially mimicked by adjusting Ca2+ levels in E3 medium. As an in vivo model, zebrafish embryos were exposed to variable Ca2+ levels (NV, normal Ca2+; LV, low Ca2+; HV, high Ca2+) alone or combined with 30.7 µg/L Cd2+ (NC, LC, and HC, respectively) until 144 hr post-fertilization. The genome-wide transcriptome revealed differentially expressed genes between groups. Functional enrichment analysis found that biological processes related to metabolism, particularly lipid metabolism, were significantly disrupted in NC and LC treatments, while a remission was observed in the HC group. Biochemical assays confirmed that the decrease in Ca2+ enhanced synthesis, inhibited mobilization and increased the storage of lipids in Cd2+ treatments. This study suggests that the toxic effect of Cd on biological pathways will be influenced by Ca2+, which will improve the toxicological understanding and facilitate accurate assessment of Cd.

Parental and transgenerational impairments of thyroid endocrine system in zebrafish by 2,4,6-tribromophenol.

Many environmental contaminants could be transmitted from parents and generate impairments to their progeny. The 2,4,6-tribromophenol (TBP), a novel brominated flame retardant which has been frequently detected in various organisms, was supposed to be bioaccumulated and intergenerational transmitted in human beings. Previous studies revealed that TBP could disrupt thyroid endocrine system in zebrafish larvae. However, there is no available data regarding the parental and transgenerational toxicity of this contaminant. Thus, in this study adult zebrafish were exposed to environmental contaminated levels of TBP for 60 days to investigate the parental and transgenerational impairments on thyroid endocrine system. Chemical analysis verified the bioaccumulation of TBP in tested organs of parents (concentration: liver>gonads>brain) and its transmission into eggs. For adults, increased thyroid hormones, disturbed transcriptions of related genes and histopathological changes in thyroid follicles indicate obvious thyroid endocrine disruptions. Transgenerational effects are indicated by the increased thyroid hormones both in eggs (maternal source) and in developed larvae (newly synthesized), as well as disrupted transcriptional profiles of key genes in HPT axis. The overall results suggest that the accumulated TBP could be transmitted from parent to offspring and generate thyroid endocrine disruptions in both generations.

Antibiotic resistance genes and their links with bacteria and environmental factors in three predominant freshwater aquaculture modes.

Rapid development of aquaculture industry and increasing demand of various inputs (especially antibiotics), are suspected to promote the occurrence and spread of ARGs in aquaculture related environments. However, the occurrences of ARGs under different freshwater aquaculture practices are rarely known. Here, we investigated the seasonal profiles of the main ARGs, intI1 and bacteria in waters from three kinds of predominant freshwater aquaculture practices around the Honghu Lake (China), as well as their co-occurrences and interrelationships with antibiotics, heavy metals and general water quality. The results indicate that quinolone resistance genes (qnrB), tetracycline resistance genes (tetB and tetX) and sulfonamide resistance genes (sul1 and sul2) were the top five predominant ARGs with seasonal variations of abundance. Fish ponds were of the highest absolute abundances of tested ARGs than the other two modes. Crayfish ponds and their adjacent ditches shared similar ARGs profile. Different subtypes of ARGs belonging to the same class of resistance were varied in abundances. Some bacteria were predicted to carry different ARGs, which indicating multi-antibiotic resistances. Moreover, the combined environmental factors (antibiotics, heavy metals and water quality) partially shaped the profiles of ARGs and bacteria composition. Overall, this study provides new comprehensive understanding on the characterization of ARGs contamination in different freshwater aquaculture practices from the perspectives of environmental chemistry, microbiology and ecology. The results would benefit the optimization of aquaculture practices toward environmental integrity and sustainability.

Nano-TiO2 enhanced bioaccumulation and developmental neurotoxicity of bisphenol a in zebrafish larvae.

The titanium dioxide nanoparticles (n-TiO2) could enhance the bioavailability and toxicity of the coexisted organic toxicants in aquatic phase. Parental co-exposure to n-TiO2 and bisphenol A (BPA) could generate developmental neurotoxicity in unexposed zebrafish offspring. However, it remains unexplored regarding the developmental neurotoxicity in larvae fish after co-exposure during the early developmental stage. In present study, fertilized zebrafish eggs were exposed to TiO2 nanoparticles (100 µg/L), BPA (1, 4 and 20 µg/L) or their binary mixtures until 6 days post fertilization (dpf). No significant change was observed in hatching, malformation, survival and weight of the larvae among all groups. However, n-TiO2 significantly increased the body burden of BPA in the 4 and 20 µg/L co-exposure groups, depressed expression of neurodevelopment marker genes (α1-tubulin, mbp and syn2a) as well as the locomotor behavior. The current results indicate that n-TiO2 could strengthen the developmental neurotoxicity and inactive locomotion in co-exposed zebrafish larvae by promoting the bioaccumulation and bioavailability of BPA, which highlighted the similar toxic risks of developmental neurotoxicity after co-exposure at early developmental stage to that of the parental co-exposure.

Bioconcentration of 2,4,6-tribromophenol (TBP) and thyroid endocrine disruption in zebrafish larvae.

2,4,6-tribromophenol (TBP) is generally used as a brominated flame retardant but is produced in the degradation of tetrabromobisphenol-A. Although TBP is frequently detected in the environment and in various biota, including fish species, we still know little about its toxicity and environmental health risk. Here we investigated the bioconcentration and effects of TBP on the thyroid endocrine system by using zebrafish as a model. Zebrafish embryos (2 h post-fertilization, hpf) were exposed to five concentrations of TBP (0, 0.3, 1, 10, and 100 µg/L) until 144 hpf. According to our chemical analysis, TBP underwent bioconcentration in zebrafish larvae. However, acute exposure to TBP did not affect the hatching of embryos or their risk of malformation, nor the growth and survival of larvae, indicating low developmental toxicity of TBP. The whole-body thyroxine (T4) contents were significantly increased in zebrafish larvae after exposure to TBP, indicating thyroid endocrine disruption occurred. Gene transcription levels in the hypothalamic-pituitary-thyroid (HPT) axis were also examined in larvae; these results revealed that the transcription of corticotrophin-releasing hormone (crh), thyrotropin-releasing hormone (trh), and thyroid-stimulating hormone (tshß) were all significantly downregulated by exposure to TBP. Likewise, genes encoding thyronine deiodinases (dio1, dio2, and dio3a/b) and thyroid hormone receptors (trα and trß) also had their transcription downregulated in zebrafish. Further, the gene transcription and protein expression of binding and transport protein transthyretin (TTR) were significantly increased after TBP exposure. Taken together, our results suggest the bioavailability of and potential thyroid endocrine disruption by TBP in fish.

Endocrine disruption in Chinese rare minnow (Gobiocypris rarus) after long-term exposure to low environmental concentrations of progestin megestrol acetate.

Synthetic progestins are widely used pharmaceutical agents that have become common contaminants in the aquatic environment. The potential adverse effects of long-term exposure on aquatic wildlife, however, are not fully understood. The aim of this study was to investigate the endocrine disruption in Chinese rare minnow (Gobiocypris rarus) in response to megestrol acetate (MTA) exposure. Newly-hatched Chinese rare minnow larvae were exposed to MTA at a nominal concentration of either 1 ng/L (detected concentrations ranged from 0.18 to 0.93 ng/L) or 10 ng/L (detected concentrations ranged from 4.27 to 9.64 ng/L) for 6 months and the effects on growth, sex steroid hormones, gonadal histology, and steroidogenic genes expression were determined. After 6 months of exposure to a nominal concentration of 10 ng/L MTA, the body weight and condition factors were significantly increased in fish of both sexes. Exposure to a nominal concentration of 10 ng/L MTA significantly reduced plasma concentrations of estradiol and 11-ketotestosterone in female fish while also reducing testosterone and 11-ketotestosterone in male fish. Gonad histology revealed significantly reduced proportions of vitellogenic oocytes in female fish exposed to a nominal concentration of 10 ng/L MTA and induction of atretic follicles in female fish exposed to both nominal concentrations of MTA. The expression of cyp19a1a and cyp17a1 in the gonads was up-regulated in the ovaries while down-regulated in the testes. Our results indicate that MTA can induce endocrine disruption in Chinese rare minnow at the low concentrations found in contaminated environments. This indicates a potentially high ecological risk from MTA to fish populations in MTA-contaminated aquatic environments in China and may also in other regions.

Enhanced Bioconcentration of Bisphenol A in the Presence of Nano-TiO2 Can Lead to Adverse Reproductive Outcomes in Zebrafish.

Titanium dioxide nanoparticles (n-TiO2) and bisphenol A (BPA) are widespread environmental contaminants in the aquatic environment. We hypothesized that n-TiO2 may adsorb BPA, and thus modify its bioavailability and toxicity to aquatic organisms. In this study, the bioavailability and toxicity of BPA (0, 2, 20, 200 µg/L) was investigated in the presence of n-TiO2 (100 µg/L). The n-TiO2 sorbed BPA and the resulting nanoparticles were taken up by zebrafish, where they translocated to the liver, brain, and gonad tissues. Increased tissue burdens of both BPA and n-TiO2 were observed following coexposure, and they also caused a reduction in plasma concentrations of estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Plasma vitellogenin (VTG) concentrations were significantly increased in males and females upon exposure to BPA. Histological examination of the ovary and testes did not show obvious morphological alterations; however, inhibition of egg production was noted in the presence of n-TiO2. The results indicated that n-TiO2 acts as a carrier of BPA and enhances its bioconcentration in zebrafish, leading to endocrine disruption and impairment of reproduction.

The neurotoxicity of DE-71: effects on neural development and impairment of serotonergic signaling in zebrafish larvae.

The underlying mechanism of polybrominated diphenyl ether (PBDE)-induced neurotoxicity is still a major concern due to its ubiquitous nature and persistence. Here, zebrafish embryos (2 h postfertilization, hpf) were exposed to different concentrations of the commercial PBDE mixture DE-71 (0-100 µg l-1 ) until 120 hpf, and the impact on neural development and serotonergic system was investigated. The in vivo results revealed significantly reduced transcription of genes involved in neurogenesis (fgf8, shha, wnt1), and contents of proteins in neuronal morphogenesis (myelin basic protein, synapsin IIa), suggesting an impairment of neural development in zebrafish embryos. Further results demonstrated a reduction of 5-hydroxytryptamine neuron and a dose-dependent decrease of whole-body serotonin levels, as well as the transcription of genes involved in serotonergic synthesis (tph1, tph2, trhr) and neurotransmission (serta/b, htr1aa/b). In addition, we predicted possible targets of PBDEs by molecular docking, and the results indicated that PBDE congeners showed high binding affinities with fibroblast growth factor 8 other than SHH and HTR1B. Taken together, this study demonstrated that PBDE exposure during embryogenesis could damage neural development and cause impairment of the serotonergic system as secondary effects in the zebrafish larvae. Copyright © 2016 John Wiley & Sons, Ltd.

Bioconcentration and transfer of the organophorous flame retardant 1,3-dichloro-2-propyl phosphate causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish larvae.

Organophosphate flame retardants are emerging environmental contaminants, although knowledge of their health risks is limited. Here, thyroid hormone homeostasis and neuronal development was studied in the progeny of adult zebrafish exposed to tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Adult zebrafish were exposed to TDCPP (0, 4, 20, and 100 µg/L) for 3 months. Increased generation of reactive oxygen species and reduced survival rates was observed in exposed F1 larvae. We also observed a significant decrease in plasma thyroxine and 3,5,3'-triiodothyronine levels in F0 females and F1 eggs/larvae. The mRNA and protein expression of factors associated with neuronal development (e.g., α1-tubulin, myelin basic protein, and synapsin IIa) were significantly downregulated in exposed F1 larvae, as was the level of the neurotransmitters dopamine, serotonin, gamma amino butyric acid, and histamine. Larval locomotion was significantly decreased in exposed fish, but there was no effect on acetylcholinesterase activity. Bioconcentration of TDCPP was observed in F0 fish. TDCPP was also detected in F1 eggs following parental exposure, indicating maternal transfer of this compound. This study uniquely shows that TDCPP can be transferred to the offspring of exposed adults, causing thyroid endocrine disruption and developmental neurotoxicity.

Detrimental effects of glyphosate on muscle metabolism in grass carp (Ctenopharyngodon idellus).

Glyphosate, a commonly used herbicide, has been associated with environmental pollution and potential health risks to aquatic organisms. This study investigated the effects of glyphosate on the muscle metabolism of grass carp (Ctenopharyngodon idellus) following exposure to environmentally relevant concentrations. Over a 14-day exposure period to varying glyphosate levels, significant disruptions were observed in antioxidant capacity and muscle health. These disruptions were evidenced by reductions in total antioxidant capacity (T-AOC), increases in malondialdehyde (MDA) levels, and decreases in activities of glutathione peroxidase (GSH-PX) and catalase (CAT). Furthermore, exposure to glyphosate resulted in a reduction of vitamin E content and an elevation of hormonal levels, suggesting the potential for endocrine disruption. Metabolomics analysis identified 605 distinct metabolites, with notable alterations in amino acid, carbohydrate, and nucleotide metabolism pathways. Specifically, arginine and glutathione metabolisms were severely impacted, with decreases in key amino acids such as glycine and glutathione at higher glyphosate concentrations. Nucleotide metabolism, particularly purine synthesis, was also significantly affected, with reduced levels of deoxyguanosine and other purine-related compounds. The study further investigated the origins of these differential metabolites using the MetOrigin platform, suggesting a potential involvement of the intestinal microbiota in the metabolic response to glyphosate. These findings highlight the multifaceted adverse effects of glyphosate on fish muscle, including oxidative stress and metabolic dysregulation, which may contribute to diminished muscle quality and health risks for aquatic organisms.

Subchronic oral toxic effects of 2,4-dinitroaniline in wistar rats: A comprehensive toxicity evaluation.

2,4-dinitroaniline (2,4-D), a widely used dye intermediate, is one of the typical pollutants, and its potential health risks and toxicity are still largely unknown. To explore its subchronic oral toxicity, Wistar rats (equal numbers of males and females) were used as test animals, and a 90-day oral dosing experiment was conducted, divided into control group, low-dose group (0.055 mg/kg), medium-dose group (0.22 mg/kg), medium-high dose group (0.89 mg/kg), and high-dose group (3.56 mg/kg). The body weight data, clinical appearance, and drug reactions of each test rat within 90 days of dosing were recorded; morning urine samples were collected four times to test for eight urinary indicators; blood samples were collected to test for nineteen hematological indicators and sixteen biochemical indicators; tissue samples were collected for pathological analysis; moreover, the no-observed-adverse-effect level (NOAEL) was determined, and the benchmark dose method was used to support this determination and provide a statistical estimate of the dose corresponding. The results indicated that the chronic toxicity of 2,4-dinitroaniline showed certain gender differences, with the eyes, liver, and kidneys being the main potential target organs of toxicity. Moreover, the subchronic oral NOAEL for 2,4-dinitroaniline was determined to be 0.22 mg/kg body weight (0.22 mg/kg for males and 0.89 mg/kg for females), and a preliminary calculation of the safe exposure limit for human was 0.136 mg/kg. The research results greatly enriched the safety evaluation data of 2,4-dinitroaniline, contributing to a robust scientific foundation for the development of informed safety regulations and public health precautions.

Life-time exposure to decabromodiphenyl ethane (DBDPE) caused transgenerational epigenetic alterations of thyroid endocrine system in zebrafish.

Because of its ubiquitous occurrence in the environment, decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, has been widely concerned. However, its transgenerational thyroid disrupting potential and intricate mechanism are barely explored. Therefore, zebrafish embryos were exposed to environmentally relevant concentrations of DBDPE (0, 0.1, 1 and 10 nM) until sexual maturity. The results indicated that life-time exposure to DBDPE caused anxiety-like behavior in unexposed offspring. Furthermore, the changing of thyroid hormones as well as transcriptional and DNA methylation level in the promoter region of related genes were evaluated. The thyroid disruptions observed in F1 larvae were primarily attributed to excessive transfer of thyroid hormone from F0 adults to F1 eggs. Conversely, the disruptions in F2 larvae were likely due to inherited epigenetic changes, specifically hypomethylation of crh and hypermethylation of ugt1ab, passed down from the F1 generation. Additionally, our results revealed sex-specific responses of the hypothalamic-pituitary-thyroid (HPT) axis in adult zebrafish. Furthermore, thyroid disruptions observed in unexposed offspring were more likely inherited from their mothers. The current results prompted our in-depth understanding of the multi- and transgenerational toxicity by DBDPE, and also highlighted the need to consider their adverse effects on persistent and inheritable epigenetic changes in future research on emerging pollutants.

An In Vitro and In Vivo Study of Thyroid Disruption of 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE)-A Novel Brominated Flame Retardant.

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), is an emerging environmental pollutant with undetermined toxicity. We investigated how BTBPE causes thyroid endocrine disruption with integrated in silico, in vitro, and in vivo assays. In yeast two-hybrid and T-Screen assays, BTBPE interacted with zebrafish thyroid hormone receptors with binding energies weaker than the TR agonist-3,3',5-Triiodo-l-thyronine (T3), and disrupted thyroid function as a thyroid receptor (TR) agonist. We examined the bioconcentration, developmental toxicity, and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE (1, 3, 10 µg/L). Thyroxine (T4) was lower in BTBPE-treated larvae, whereas corticotropin-releasing hormone (CRH) and thyroid-stimulating hormone (TSH) were higher. The gene transcription alterations along the hypothalamic-pituitary-thyroid (HPT) axis were observed. Furthermore, reduced locomotion suggested that BTBPE imparts developmental neurotoxicity at zebrafish early developmental stage. Establishing that BTBPE has thyroid endocrine-disrupting effects is an important step for understanding and managing BTBPE toxicity.

Aggravated visual toxicity in zebrafish larvae upon co-exposure to titanium dioxide nanoparticles and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate.

The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO2 or TBPH significantly suppressed the expression of ßB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates.

Behavioral impairments and disrupted mitochondrial energy metabolism induced by polypropylene microplastics in zebrafish larvae.

Polypropylene microplastics (PP-MPs) are emerging pollutant commonly detected in various environmental matrices and organisms, while their adverse effects and mechanisms are not well known. Here, zebrafish embryos were exposed to environmentally relevant concentrations of PP-MPs (0.08-50 mg/L) from 2 h post-fertilization (hpf) until 120 hpf. The results showed that the body weight was increased at 2 mg/L, heart rate was reduced at 0.08 and 10 mg/L, and behaviors were impaired at 0.4, 10 or 50 mg/L. Subsequently, transcriptomic analysis in the 0.4 and 50 mg/L PP-MPs treatment groups indicated potential inhibition on the glycolysis/gluconeogenesis and oxidative phosphorylation pathways. These findings were validated through alterations in multiple biomarkers related to glucose metabolism. Moreover, abnormal mitochondrial ultrastructures were observed in the intestine and liver in 0.4 and 50 mg/L PP-MPs treatment groups, accompanied by significant decreases in the activities of four mitochondrial electron transport chain complexes and ATP contents. Oxidative stress was also induced, as indicated by significantly increased ROS levels and significant reduced activities of CAT and SOD and GSH contents. All the results suggested that environmentally relevant concentrations of PP-MPs could induce disrupted mitochondrial energy metabolism in zebrafish, which may be associated with the observed behavioral impairments. This study will provide novel insights into PP-MPs-induced adverse effects and highlight need for further research.

Effects of glyphosate exposure on gut-liver axis: Metabolomic and mechanistic analysis in grass carp (Ctenopharyngodon idellus).

Glyphosate, one of the most widely used herbicide worldwide, is potentially harmful to non-target aquatic organisms. However, the environmental health risks regarding impacts on metabolism homeostasis and underlying mechanisms remain unclear. Here we investigated bioaccumulation, metabolism disorders and mechanisms in grass carp after exposure to glyphosate. Higher accumulation of glyphosate and its major metabolite, aminomethylphosphonic acid, in the gut was detected. Intestinal inflammation, barrier damage and hepatic steatosis were caused by glyphosate exposure. Lipid metabolism disorder was confirmed by the decreased triglyceride, increased total cholesterol and lipoproteins in serum and decreased visceral fat. Metabolomics analysis found that glyphosate exposure significantly inhibited bile acids biosynthesis in liver with decreased total bile acids content, which was further supported by significant downregulations of cyp27a1, cyp8b1 and fxr. Moreover, the dysbiosis of gut microbiota contributed to the inflammation in liver and gut by increasing lipopolysaccharide, as well as to the declined bile acids circulation by reducing secondary bile acids. These results indicated that exposure to environmental levels of glyphosate generated higher bioaccumulation in gut, where evoked enterohepatic injury, intestinal microbiota dysbiosis and disturbed homeostasis of bile acids metabolism; then the functional dysregulation of the gut-liver axis possibly resulted in ultimate lipid metabolism disorder. These findings highlight the metabolism health risks of glyphosate exposure to fish in aquatic environment.

Tris(1,3-dichloro-2-propyl) phosphate causes female-biased growth inhibition in zebrafish: Linked with gut microbiota dysbiosis.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is ubiquitous in aquatic environment, but its effect on intestinal health of fish has yet not been investigated. In the present study, the AB strain zebrafish embryos were exposed to environmentally realistic concentrations (0, 30, 300, and 3000 ng·L-1) of TDCIPP for 90 days, after which the fish growth and physiological activities were evaluated, and the intestinal microbes were analyzed by 16S rRNA gene high-throughput sequencing. Our results manifested that the body length and body weight were significantly reduced in the female zebrafish but not in males. Further analyses revealed that TDCIPP resulted in notable histological injury of intestine, which was accompanied by impairment of epithelial barrier integrity (decreased tight junction protein 2), inflammation responses (increased interleukin 1ß), and disruption of neurotransmission (increased serotonin) in female intestine. Male intestines maintained intact intestinal structure, and the remarkably increased activity of glutathione peroxidase (GPx) might protect the male zebrafish from inflammation and intestinal damage. Furthermore, 16S rRNA sequencing analysis showed that TDCIPP significantly altered the microbial communities in the intestine in a gender-specific manner, with a remarkable increase in alpha diversity of the gut microbiome in male zebrafish, which might be another mechanism for male fish to protect their intestines from damage by TDCIPP. Correlation analysis revealed that abnormal abundances of pathogenic bacteria (Chryseobacterium, Enterococcus, and Legionella) might be partially responsible for the impaired epithelial barrier integrity and inhibition in female zebrafish growth. Taken together, our study for the first time demonstrates the high susceptibility of intestinal health and gut microbiota of zebrafish to TDCIPP, especially for female zebrafish, which could be partially responsible for the female-biased growth inhibition.