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Highlights: [•] MCLR significantly impaired LTP in a concentration-dependent manner. [•] GSK-3β inhibitors prevents the effects of MCLR on hippocampal LTP in vivo. [•] MCLR increased the activity of GSK-3β via regulating phosphorylation at Ser9 site. [Copyright &y& Elsevier]

Selenium (Se), an indispensable micronutrient for living organisms, has been extensively studied for its heavy metal-detoxifying properties in diverse biological systems and tissues. Nevertheless, it is not entirely certain whether Se can effectively protect against Cadmium (Cd)-induced gut inflammation, especially in aquatic animals. In this study, we employed various approaches, including transcriptome profiling, histological examinations, assessment of antioxidant enzyme activities, and analysis of gut microbiota composition to investigate the effects on crayfish growth and intestinal health after exposure to dietary Cd (15 mg kg−1 diet) and Se (15 mg kg−1 diet) individually or in combination for 8 weeks. The results revealed that dietary Cd exposure resulted in reduced body weight and survival rates, along with an increased occurrence of intestinal inflammation. Nevertheless, Se supplementation proved effective in mitigating the adverse effects of Cd on growth and gut health. Se exhibited a remarkable ability to counteract the disruption of gut antioxidant abilities induced by dietary Cd, as evidenced by the observed increases in ROS and MDA contents, decrease in GSH levels, and inhibition of antioxidative enzyme activities. At the concentration of 6 mg kg−1 in the diet, Se was found beneficial for maintaining gut microbiota richness and diversity. Among them, Flavobacterium , Thermomonas , and Chloronema displayed a weak negative correlation with the rate of gut inflammation. Meanwhile, the levels of short chain fatty acids (SCFAs), including acetic acid (AA) and butanoic acid (BA), showed a significant increase in the Se–Cd group compared to the Cd-only group. Furthermore, transcriptome analysis exhibited significant responses of the PI3K/Akt and NF-κB pathways following crayfish exposure to dietary Se and Cd, either separately or in combination. In short, this study provides a new evidence regarding the molecular mechanisms through which Se could regulate the PI3K/Akt and NF-κB pathways, either directly or indirectly via ROS and SCFAs, thereby alleviating Cd-induced gut inflammation in crayfish. [Display omitted] • Chronic Cd exposure (15 mg/kg) markedly induced gut inflammation and apoptosis. • Cd decreased crayfish weight and survival, but Se supplementation mitigated this. • Se countered the disruption of gut antioxidant capabilities induced by dietary Cd. • Se antagonized Cd-induced gut inflammation by boosting SCFA content. • PI3K/Akt/NF-κB pathways mediated Se's counteraction of Cd toxicity in the gut. [ABSTRACT FROM AUTHOR]

Several mechanisms regarding the developmental and reproductive toxicity of l -selenomethionine (SeMet) in freshwater fish have been widely reported. However, limited information was available on endocrine-disrupting effects of SeMet. In this study, zebrafish larvae (day 24 post-fertilization) were exposed to environmentally-relevant levels of dietary SeMet (control, 1.11 ± 0.11, 3.59 ± 0.20, 10.80 ± 0.52, 29.19 ± 0.46, and 58.63 ± 0.70 μg Se/g d.w. diet) for 90 days until sexual maturity. For the first time, a gender difference in the effect of SeMet on body mass of zebrafish was observed. The lowest observed adverse effect level (LOAEL) in male was 10.80 ± 0.52 μg Se/g d.w., while it was 29.19 ± 0.46 μg Se/g d.w. in female. Chronic exposure to dietary SeMet reduced the percentage of early vitellogenic oocyte in female and the percentage of spermatid in male by inhibiting the growth hormone/insulin-like growth factors (GH/IGFs) and hypothalamus-pituitary-gonad (HPG) systems, which was characterized by significant decreases in the transcriptional levels of gh , igf1 , era , and ar. Se content in the liver of male was significantly higher than that in female when dietary Se level reached 10.80 ± 0.52 μg Se/g d.w.. Furthermore, the zinc content in the livers and gonads of both female and male treated with 29.19 ± 0.46 and 58.63 ± 0.70 μg Se/g d.w. diets was significantly reduced. Reduction of zinc ion not only led to the significantly upregulated transcriptional levels of zip1 and znt2 , but also downregulated transcriptional levels of znf219l and sp7. In summary, this study provides a new evidence that chronic exposure to high level of dietary SeMet (≥10.80 μg Se/g d.w.) could impair the development and reproduction of zebrafish with gender difference by interfering the GH/IGFs and HPG systems. Moreover, disruption of zinc ion homeostasis might exacerbate the toxicity of Se to zebrafish. Image 1 • The LOAEL in male was 10.80 μg Se/g, while it was 29.19 μg Se/g in female. • SeMet impaired growth and reproduction by interfering GH/IGFs and HPG systems. • Chronic exposure to high level of dietary SeMet disrupted zinc ion homeostasis. [ABSTRACT FROM AUTHOR]

Abstract Pentachlorophenol (PCP) and its byproduct hexachlorobenze (HCB) are two co-existing persistent environmental chemicals, but their combined toxicity remains unclear. In this study, adult zebrafish were exposed to 5 (low dose) and 25 μg·L−1 (high dose) of PCP, HCB or their combination for 21 days, and the impact on endocrine and reproduction was investigated. Results showed that combined exposure to 25 μg·L−1 PCP and 25 μg· L−1 HCB significantly increased the plasma estradiol (E2) and testosterone (T) levels, altered the expressions of genes along the hypothalamic-pituitary-gonadal-liver (HPGL) axis, inhibited gonadal development, and eventually lead to decreased egg production of F0 zebrafish as well as inhibited development of F1 eggs/larvae. Compared to the combined exposure of high doses, significantly lower levels of plasma E2 and T were observed for either the high PCP or high HCB alone exposure, indicating a synergistic effect of the two chemicals on endocrine disruption after combination. Furthermore, the high PCP alone exposure inhibited the gonadal development in both the males and females, while the HCB alone exposure did not. Comparison of exposure effects indicated a greater decrease of mature gametes levels and egg production in the high combined group when compared to the high HCB alone group, but no significant difference was observed between the high combined group and the high PCP alone group. Taken together, the results suggested that combined exposure to PCP and HCB may synergistically affect endocrine of zebrafish, and result in reproduction impairments, with PCP being the primary contributor. Highlights • Combined exposure to PCP and HCB resulted in reproductive impairments in zebrafish. • Combined exposure to PCP and HCB may synergistically affect endocrine of zebrafish. • Decreased GSI value and inhibited gonadal development in females might be associated with the decrease of egg production. • Reproductive impairments in the high combined group may be more attributable to the PCP toxicity. [ABSTRACT FROM AUTHOR]

Abstract Tris (2-butoxyethyl) phosphate (TBOEP) is a ubiquitous environmental contaminant due to its overuse. TBOEP has been found to cause reproductive toxicity and endocrine disruption during acute toxic experiment. In this study, we examined the effects of TBOEP on growth in initial generation (F0) zebrafish and transgenerational effects on growth of first generation (F1) larvae after parental long-term exposure (120 d) to environmentally relevant concentrations (0, 0.1, 1, 10 and 100 μg/L). Exposure to TBOEP resulted in significantly less growth as measured by body length, body weight and gonadosomatic index (GSI) in F0 females but not F0 males. Furthermore, the bioaccumulation of TBOEP in gonad, the alteration of the gene transcriptions in the hypothalamic-pituitary-gonadal (HPG) axis, and the delay in gonadal development in both female and male zebrafish were demonstrated. In addition, the residues of TBOEP were detected in F1 larvae after parental exposure, resulting in lower survival and shorter body length, as well as faster heart rate. And no significant changes in gene expressions along the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis were found in F1 larvae. In conclusion, these results indicated that long-term parental exposure to environmentally relevant concentrations of TBOEP could inhibit the development of progeny by parental gonadal impairment and by TBOEP transfer to offspring, instead of gene transcription in GH/IGF and HPT axes. Highlights • TBOEP caused significantly less growth in F0 females but not F0 males. • TBOEP at environmentally relevant concentrations caused gonadal impairment. • The residues of TBOEP were detected in F1 larvae after exposure of parents. • Long-term parental exposure to TBOEP inhibited the development of progeny. [ABSTRACT FROM AUTHOR]

Abstract Tris (2-butoxyethyl) phosphate (TBOEP), as one of the most widely used organophosphate flame retardants (OPFRs), is applied in nearly all manufactured items and materials. It has been reported that TBOEP could cause developmental impairments and disrupt the endocrine regulation of fish growth during acute toxic experiments. However, concentrations to which fish were exposed in these studies were greater than environmentally relevant concentrations ever reported. This study examined effects on growth associated with exposure of zebrafish to 0, 0.1, 1 and 10 μg/L TBOEP during 20–90 days post fertilization (dpf). The changes in growth indicators and bioaccumulation of TBOEP were examined along with the transcription of related genes in the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis. The average body contents of TBOEP were higher in females than in males in all the exposure groups. Exposure to environmentally relevant concentrations of TBOEP significantly decreased body length and body mass and down-regulated expression of several genes involved in the GH/IGF and HPT axes. Exposure to TBOEP decreased plasma thyroxine (T4) content accompanied by decreased mRNA level of thyrotropin β-subunit (tshβ) in females at 60 dpf, but no effects were observed at 90 dpf. These results suggested that bioaccumulation of TBOEP and down-regulation of genes involved in the GH/IGF axis might be responsible for the observed growth inhibition in zebrafish exposed to TBOEP. Highlights • Growth of zebrafish was inhibited by environmentally relevant levels of TBOEP. • TBOEP had no persistent effect on concentrations of THs. • Bioaccumulation of TBOEP contributed to the growth inhibition. • Disruption of GH/IGF axis was induced by environmentally relevant levels of TBOEP. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that cyanobacteria-derived Microcystin-LR (MC-LR) can cause developmental toxicity and trigger apoptosis in zebrafish ( Danio rerio ) larvae, but the underlying mechanisms remain largely unknown. In this study, we tested the hypothesis that the mechanism by which MC-LR induces developmental toxicity is through activation of endoplasmic reticulum (ER) stress. MC-LR (4.0 μM) exposure through submersion caused serious developmental toxicity, such as malformation, growth delay and decreased heart rates in zebrafish larvae, which could be inhibited by ER stress blocker, tauroursodeoxycholic acid (TUDCA, 20 μM). Meanwhile, acridine orange (AO) staining showed TUDCA could rescue cell apoptosis in heart area in zebrafish larvae resulted by MC-LR exposure. Real-time polymerase chain reaction (real-time PCR) analysis demonstrated that MC-LR induced activation of ER stress which consequently triggered apoptosis in zebrafish larvae. Protein expression examined by western blot indicated that MC-LR could activate MAPK8/Bcl-2/Bax pathway and caspase-dependent apoptotic pathway in zebrafish larva and the effects were mitigated by inhibition of ER stress. Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR. [ABSTRACT FROM AUTHOR]

Abstract: Microcystin–leucine–arginine (MCLR) is the most toxic and the most commonly encountered variant of microcystins (MCs) in aquatic environment, and it has the potential for disrupting thyroid hormone homeostasis, but the molecular mechanisms underlying this process have not yet been clarified. In the present study, we observed body growth retardation associated with decreased levels of thyroid hormones (THs) in zebrafish larvae, highlighting the interferences of MCLR with the growth of fish larvae. To further our understanding of mechanisms of MCLR-induced endocrine toxicity, quantitative real-time PCR analysis was performed on hypothalamic–pituitary–thyroid (HPT) axis related genes of developing zebrafish embryos exposed to 100, 300 and 500μgL−1 MCLR until 96h post-fertilization. The expression of several genes in the HPT system, i.e., corticotropin-releasing factor (CRF), thyroid-stimulating hormone (TSH), sodium/iodide symporter (NIS), thyroglobulin (TG), thyroid receptors (TRα and TRβ) and iodothyronine deiodinases (Dio1 and Dio2) was examined using quantitatively real-time PCR. The gene expression levels of CRF, TSH, NIS and TG were significantly induced after exposure to 500μgL−1 MCLR. The transcription of TRs gene was down-regulated in a concentration-dependent manner. Up-regulation and down-regulation of Deio1 and Deio2 gene expression, respectively, were observed upon exposure to MCLR. The above results indicated that MCLR could alter gene expression in the HPT axis which might subsequently contribute to MCLR-induced thyroid disruption. [Copyright &y& Elsevier]

Microcystin-LR (MCLR) was commonly regarded as a potent hepatotoxin and has been reported to cause neurotoxicity. This study was aimed to investigate how maternal MCLR exposure during pregnancy alters behavioral responses in offspring mice and the possible molecular mechanism involved in this procedure. Three doses of MCLR solutions (0, 3 or 15 μg/kg body weight) were administered subcutaneously to pregnant C57bl/6 from gestation day (GD) 6–19. Our results showed that MCLR prenatal exposure led to the impairment of learning and memory function in offspring on postnatal days (PND) 35, accompanied by endoplasmic reticulum (ER) stress and neuronal apoptosis in hippocampal CA1 regions of mice. Sixteen miRNAs in hippocampus of pups on PND 35 were significantly affected by MCLR exposure with the markedly decreased transcription of miR-181a-5p. We then found that miR-181a-5p was down-regulated, accompanied by activation of ER stress after prenatal exposure to MCLR using qPCR analysis. Furthermore, glucose-regulated protein, 78kDa/binding immunoglobulin protein (Grp78/BIP), a major ER chaperone and signaling regulator, was identified as a target of miR-181a-5p. Our study showed that miR-181a could lead to a decrease in the mRNA expression and protein levels of Grp78 by directly binding to its 3′-untranslated region (3′-UTR) in primary hippocampal neurons. Our findings indicate that the up-regulation of Grp78 mediated by inhibition of miR-181a-5p is a possible mechanism resulting in ER stress and cognitive impairment in pups following prenatal MCLR exposure. • Maternal MC-LR exposure altered behavioral responses in offspring mice. • MC-LR prenatal exposure led to endoplasmic reticulum (ER) stress and neuronal apoptosis in offspring. • Inhibition in miR-181a resulted in the activation of ER stress and subsequent apoptosis. [ABSTRACT FROM AUTHOR]