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Reproductive dysfunction linked to alteration of endocrine activities in zebrafish exposed to mono-(2-ethylhexyl) phthalate (MEHP) 全文
2020
Park, Chang-Beom | Kim, Ko-ŭn | Kim, Yŏng-jun | On, Jiwon | Pak, Ch'ang-gyun | Kwon, Young-Sang | Pyo, Heesoo | Yeom, Dong-Huk | Cho, Sung Hee
This study aimed to investigate the effect of mono-(2-ethylhexyl) phthalate (MEHP), one of the major phthalate metabolites that are widespread in aquatic environments, on reproductive dysfunction, particularly on endocrine activity in adult male and female zebrafish. For 21 days, the zebrafish were exposed to test concentrations of MEHP (0, 2, 10, and 50 μg/mL) that were determined based on the effective concentrations (ECx) for zebrafish embryos. Exposure to 50 μg/mL MEHP in female zebrafish significantly decreased the number of ovulated eggs as well as the hepatic VTG mRNA abundance when those of the control group. Meanwhile, in female zebrafish, the biosynthetic concentrations of 17β-estradiol (E2) and the metabolic ratio of androgen to estrogen were remarkably increased in all MEHP exposed group compared with those in the control group, along with the elevated levels of cortisol. However, no significant difference was observed between these parameters in male zebrafishes. Therefore, exposure to MEHP causes reproductive dysfunction in female zebrafishes and this phenomenon can be attributed to the alteration in endocrine activities. Moreover, the reproductive dysfunction in MEHP-exposed female zebrafishes may be closely associated with stress responses, such as elevated cortisol levels. To further understand the effect of MEHP on the reproductive activities of fish, follow-up studies are required to determine the interactions between endocrine activities and stress responses. Overall, this study provides a response biomarker for assessing reproductive toxicity of endocrine disruptors that can serve as a methodological approach for an alternative to chronic toxicity testing.
显示更多 [+] 显示较少 [-]Influence of dietary iron exposure on trace metal homeostasis and expression of metal transporters during development in zebrafish☆ 全文
2020
Chandrapalan, Theanuga | Kwong, Raymond W.M.
The present study investigated the effects of dietary iron (Fe) exposure on physiological performance and homeostatic regulation of trace metals during development (5–28 days post-fertilization; dpf) in zebrafish (Danio rerio). The results demonstrated that whole body Fe content was increased in 14 dpf larvae fed a high Fe diet. Cumulative mortality was also significantly elevated during exposure to the high Fe diet. Using droplet digital PCR, we observed that high Fe-exposed larvae exhibited an increase in mRNA levels of the Fe-storage protein ferritin, which appeared to be associated with the elevated level of whole body Fe content. Further, the results indicated that dietary Fe exposure induced transient changes in the mRNA expression levels of various metal transporters, including the iron transporter dmt1, and the zinc transporters zip8 and zip14. The expression of the epithelial Ca²⁺ channels (i.e., ecac) was also found to increase by high dietary Fe. Overall, our findings suggest that larval fish during the early nutritional transition period are sensitive to the effects of dietary Fe.
显示更多 [+] 显示较少 [-]Effects of gestational Perfluorooctane Sulfonate exposure on the developments of fetal and adult Leydig cells in F1 males 全文
2020
Studies have showed that some of the most common male reproductive disorders present in adult life might have a fetal origin. Perfluorooctane sulfonic (PFOS) is one of the major environmental pollutants that may affect the development of male reproductive system if exposed during fetal or pubertal periods. However, whether PFOS exposure during fetal period affects testicular functions in the adult is still unclear. Herein, we investigated the effects of a brief gestational exposure to PFOS on the development of adult Leydig- and Sertoli-cells in the male offspring. Eighteen pregnant Sprague-Dawley rats were randomly divided into three groups and each received 0, 1 or 5 mg/kg/day PFOS from gestational day 5–20. The testicular functions of F1 males were evaluated on day 1, 35 and 90 after birth. PFOS treatment significantly decreased serum testosterone levels of animals by all three ages examined. The expression level of multiple mRNAs and proteins of Leydig (Scarb1, Cyp11a1, Cyp17a1 and Hsd17b3) and Sertoli (Dhh and Sox9) cells were also down-regulated by day 1 and 90. PFOS exposure might also inhibit Leydig cell proliferation since the number of PCNA-positive Leydig cells were significantly reduced by postnatal day 35. Accompanied by changes in Leydig cell proliferation and differentiation, PFOS also significantly reduced phosphorylation of glycogen synthase kinase-3β while increased phosphorylation of β-catenin. In conclusion, gestational PFOS exposure may have significant long-term effects on adult testicular functions of the F1 offspring. Changes in Wnt signaling may play a role in the process.
显示更多 [+] 显示较少 [-]Chronic exposure to environmentally relevant concentrations of bisphenol S differentially affects cognitive behaviors in adult female zebrafish 全文
2020
Naderi, Mohammad | Salahinejad, Arash | Attaran, Anoosha | Chivers, Douglas P. | Niyogi, Som
Evidence is emerging that environmental exposure to bisphenol S (BPS), a substitute for bisphenol A (BPA), to humans and wildlife is on the rise. However, research on the neurobehavioral effects of this endocrine disruptive chemical is still in its infancy. In this study, we aimed to investigate the effects of long-term exposure to environmentally relevant concentrations of BPS on recognition memory and its mechanism(s) of action, especially focusing on the glutamatergic/ERK/CREB pathway in the brain. Adult female zebrafish were exposed to the vehicle, 17β-estradiol (E2, 1 μg/L), or BPS (1, 10 and 30 μg/L) for 120 days. Fish were then tested in the object recognition (OR), object placement (OP), and social recognition tasks (SR). Chronic exposure to E2 and 1 μg/L of BPS improved fish performance in OP task. This was associated with an up-regulation in the mRNA expression of several subtypes of metabotropic and ionotropic glutamate receptors, an increase in the phosphorylation levels of ERK1/2 and CREB, and an elevated transcript abundance of several immediate early genes involved in synaptic plasticity and memory formation. In contrast, the exposure to 10 and 30 μg/L of BPS attenuated fish performance in all recognition memory tasks. The impairment of these memory functions was associated with a marked down-regulation in the expression and activity of genes and proteins involved in glutamatergic/ERK/CREB signaling cascade. Collectively, our study demonstrated that the long-term exposure to BPS elicits hermetic effects on the recognition memory in zebrafish. Furthermore, the effect of BPS on the recognition memory seems to be mediated by the glutamatergic/ERK/CREB signaling pathway.
显示更多 [+] 显示较少 [-]SFPQ is involved in regulating arsenic-induced oxidative stress by interacting with the miRNA-induced silencing complexes 全文
2020
Guo, Ping | Chen, Shen | Li, Daochuan | Zhang, Jinmiao | Luo, Jiao | Zhang, Aihua | Yu, Dianke | Bloom, Michael S. | Chen, Liping | Chen, Wen
Arsenic exposure contributed to the development of human diseases. Arsenic exerted multiple organ toxicities mainly by triggering oxidative stress. However, the signaling pathway underlying oxidative stress is unclear. We previously found that the expression of SFPQ, a splicing factor, was positively associated with urinary arsenic concentration in an arsenic-exposed population, suggesting an oxidative stress regulatory role for SFPQ. To test this hypothesis, we established cell models of oxidative stress in human hepatocyte cells (L02) treated with NaAsO₂. Reactive oxygen species (ROS) synthesis displayed a time- and dose-dependent increase with NaAsO₂ treatment. SFPQ suppression resulted in a 36%–53% decrease in ROS generation, leading to enhanced cellular damage determined by 8-OHdG, comet tail moment, and micronucleus analysis. Particularly, SFPQ deficiency attenuated expression of the oxidase genes DUOX1, DUOX2, NCF2, and NOX2. A fluorescent-based RNA electrophoretic mobility shift assay (FREMSA) and dual-luciferase reporter system revealed that miR-92b-5p targeted DUOX2 mRNA degradation. An RNA immunoprecipitation assay showed an interaction between SFPQ and miR-92b-5p of the miRNA-induced silencing complex (miRISC). Notably, NaAsO₂ treatment diminished the interaction between SFPQ and miR92b-5p, accompanied by decreased binding between miR-92b-5p and 3′-UTR of DUOX2. However, SFPQ deficiency suppressed the dissociation of miR-92b-5p from 3′-UTR of DUOX2, indicating that miR-92b-5p regulated the SFPQ-dependent DUOX2 expression. Taken together, we reveal that SFPQ responds to arsenic-induced oxidative stress by interacting with the miRISC. These findings offer new insight into the potential role of SFPQ in regulating cellular stress response.
显示更多 [+] 显示较少 [-]High carbohydrate diet partially protects Nile tilapia (Oreochromis niloticus) from oxytetracycline-induced side effects 全文
2020
Limbu, Samwel Mchele | Zhang, Han | Luo, Yuan | Chen, Li-Qiao | Zhang, Meiling | Du, Zhen-Yu
Antibiotics used in global aquaculture production cause various side effects, which impair fish health. However, the use of dietary composition such as carbohydrate, which is one of the dominant components in fish diets to attenuate the side effects induced by antibiotics, remains unclear. We determined the ability of high carbohydrate diet to protect Nile tilapia (Oreochromis niloticus) from oxytetracycline-induced side effects. Triplicate groups of thirty O. niloticus (9.50 ± 0.08 g) were fed on medium carbohydrate (MC; 335 g/kg) and high carbohydrate (HC; 455 g/kg) diets without and with 2.00 g/kg diet of oxytetracycline (80 mg/kg body weight/day) hereafter, MCO and HCO for 35 days. Thereafter, we assessed growth performance, hepatic nutrients composition and metabolism, microbiota abundance, immunity, oxidative and cellular stress, hepatotoxicity, lipid peroxidation and apoptosis. To understand the possible mechanism of carbohydrate protection on oxytetracycline, we assessed the binding effects and efficiencies of mixtures of medium and high starch with oxytetracycline as well as the MCO and HCO diets. The O. niloticus fed on the MCO and HCO diets had lower growth rate, nutrients utilization and survival rate than those fed on the MC and HC diets, respectively. Dietary HCO increased hepatosomatic index and hepatic protein content of O. niloticus than MCO diet. The O. niloticus fed on the HCO diet had lower mRNA expression of genes related to protein, glycogen and lipid metabolism compared to those fed on the MCO diet. Feeding O. niloticus on the HCO diet increased innate immunity and reduced pathogenic bacteria, pro-inflammation, hepatotoxicity, cellular stress and apoptosis than the MCO diet. The high starch with oxytetracycline and HCO diet had higher-oxytetracycline binding effects and efficiencies than the medium starch with oxytetracyline and MCO diet, respectively. Our study demonstrates that, high carbohydrate partially protects O. niloticus from oxytetracycline-induced side effects by binding the antibiotic. Incorporating high carbohydrate in diet formulation for omnivorous fish species alleviates some of the side effects caused by antibiotics.
显示更多 [+] 显示较少 [-]One year exposure to Cd- and Pb-contaminated soil causes metal accumulation and alteration of global DNA methylation in rats 全文
2019
Nakayama, Shouta M.M. | Nakata, Hokuto | Ikenaka, Yoshinori | Yabe, John | Oroszlany, Balazs | Yohannes, Yared B. | Bortey-Sam, Nesta | Muzandu, Kaampwe | Choongo, Kennedy | Kuritani, Takeshi | Nakagawa, Mitsuhiro | Ishizuka, Mayumi
Metal pollution has been associated with anthropogenic activities, such as effluents and emissions from mines. Soil could be exposure route of wild rats to metals, especially in mining areas. The aim of this study was to verify whether soil exposure under environmentally relevant circumstances results in metal accumulation and epigenetic modifications. Wistar rats were divided to three groups: 1) control without soil exposure, 2) low-metal exposure group exposed to soil containing low metal levels (Pb: 75 mg/kg; Cd: 0.4), and 3) high-metal exposure group exposed to soil (Pb: 3750; Cd: 6). After 1 year of exposure, the metal levels, Pb isotopic values, and molecular indicators were measured. Rats in the high-group showed significantly greater concentrations of Pb and Cd in tissues. Higher accumulation factors (tissue/soil) of Cd than Pb were observed in the liver, kidney, brain, and lung, while the factor of Pb was higher in the tibia. The obtained results of metal accumulation ratios (lung/liver) and stable Pb isotope ratios in the tissues indicated that the respiratory exposure would account for an important share of metal absorption into the body. Genome-wide methylation status and DNA methyltransferase (Dnmt 3a/3b) mRNA expressions in testis were higher in the high-group, suggesting that exposure to soil caused metal accumulation and epigenetic alterations in rats.
显示更多 [+] 显示较少 [-]Inflammatory and oxidative injury is induced in cardiac and pulmonary tissue following fipronil exposure in Japanese quail: mRNA expression of the genes encoding interleukin 6, nuclear factor kappa B, and tumor necrosis factor-alpha 全文
2019
Khalil, Samah R. | Mohammed, Wafaa A. | Zaglool, Asmaa W. | Elhady, Walaa M. | Farag, Mayada R. | El sayed, Shafika A.M.
The phenylpyrazole insecticide, fipronil, isused for the eradication of insects in agriculture, which also exposes various non-target groups such as birds and animals. Our aim was to assess the cardiac and pulmonary consequences of sub-acute administration of fipronil (¹∕₅ LD₅₀; 2.26 mg/kg) in the Japanese quail for fifteen days and to determine the tissue recovery over a period of 60 days. Fipronil exposure led to a significant decrease in the body weight of the treated birds. Its exposure also induced cardiac and pulmonary damage of varying degrees. Fipronil increased the lipid peroxide (LPO) and nitric oxide (NO) contents as well as indices of tissue injury in the serum of exposed birds. Furthermore, it decreased the antioxidant indices in both the organs. Most of these changes gradually reversed and the histological changes, particularly of the heart, reversed completely by day-60 of recovery. Furthermore, alterations in the mRNA gene expressions of Nuclear factor kappa B (NF-κB), Interleukin 6 (IL-6), and Tumor necrosis factor-alpha (TNF-α) were monitored by quantitative polymerase chain reaction (RT-PCR). In both the tissues, a significant up-regulation of the transcripts was recorded after fipronil administration, which was reversed during the recovery period in the heart tissue except for TNF-α, while the transcripts in the lung tissue declined non-significantly. This study showed that the exposure of Japanese quail to fipronil has a profound negative impact on heart and lung including oxidative injury and tissue inflammation. Fipronil can induce the activity of NF-κB inflammatory -signaling pathway that play a role in the associated tissue inflammation. Although most of the cardiac changes could be reversed after a recovery period of sixty days, the pulmonary changes did not reverse much.
显示更多 [+] 显示较少 [-]Pxr- and Nrf2- mediated induction of ABC transporters by heavy metal ions in zebrafish embryos 全文
2019
Hu, Jia | Tian, Jingjing | Zhang, Feng | Wang, Han | Yin, Jian
Transcription factors including pregnane X receptor (Pxr) and nuclear factor-erythroid 2-related factor-2 (Nrf2) are important modulators of Adenosine triphosphate-binding cassette (ABC) transporters in mammalian cells. However, whether such modulation is conserved in zebrafish embryos remains largely unknown. In this manuscript, pxr- and nrf2-deficient models were constructed with CRISPR/Cas9 system, to evaluate the individual function of Pxr and Nrf2 in the regulation of ABC transporters and detoxification of heavy metal ions like Cd²⁺ and Ag⁺. As a result, both Cd²⁺ and Ag⁺ conferred extensive interactions with ABC transporters in wild type (WT) embryos: their accumulation and toxicity were affected by the activity of ABC transporters, and they significantly induced the mRNA expressions of ABC transporters. These induction effects were reduced by the mutation of pxr and nrf2, but elevations in the basal expression of ABC transporters compensated for the loss of their inducibility. This could be an explanation for remaining transporter function in both mutant models as well as the unaltered toxicity of metal ions in pxr-deficient embryos. However, mutation of nrf2 disrupted the production of glutathione (GSH), resulting in the enhanced toxicity of Cd²⁺/Ag⁺ in zebrafish embryos. In addition, elevated expressions of other transcription factors like aryl hydrocarbon receptor (ahr) 1b, peroxisome proliferator-activated receptor (ppar)-β, and nrf2 were found in pxr-deficient models without any treatment, while enhanced induction of ahr1b, ppar-β and pxr could only be seen in nrf2-deficient embryos after the treatment of metal ions, indicating different compensation phenomena for the absence of transcription factors. After all, pxr-deficient and nrf2-deficient zebrafish embryos are useful tools in the functional investigation of Pxr and Nrf2 in the early life stages of aquatic organisms. However, the compensatory mechanisms should be taken into consideration when interpreting the results and need in-depth investigations.
显示更多 [+] 显示较少 [-]Effects of antidepressants with different modes of action on early life stages of fish and amphibians 全文
2019
Sehonova, Pavla | Hodkovicova, Nikola | Urbanova, Monika | Örn, Stefan | Blahova, Jana | Svobodová, Zdeňka | Faldyna, Martin | Chloupek, Petr | Briedikova, Kristina | Carlsson, Gunnar
Drugs are excreted from the human body as both original substances and as metabolites and enter aquatic environment through waste water. The aim of this study was to widen the current knowledge considering the effects of waterborne antidepressants with different modes of action—amitriptyline, venlafaxine, sertraline—on embryos of non-target aquatic biota—fish (represented by Danio rerio) and amphibians (represented by Xenopus tropicalis). The tested concentrations were 0.3; 3; 30; 300 and 3000 μg/L in case of amitriptyline and venlafaxine and 0.1; 1; 10; 100 and 1000 μg/L for sertraline. Test on zebrafish embryos was carried out until 144 h post fertilization, while test on Xenopus embryos was terminated after 48 h. Lethal and sublethal effects as well as swimming alterations were observed at higher tested concentrations that are not present in the environment. In contrast, mRNA expression of genes related to heart, eye, brain and bone development (nkx2.5, otx 2, bmp4 and pax 6) seems to be impacted also at environmentally relevant concentrations. In a wider context, this study reveals several indications on the ability of antidepressants to affect non target animals occupying environments which may be contaminated by such compounds.
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