| 1. |
- Bereketoglu, Ceyhun, 1982-, et al.
(författare)
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Comparative transcriptional analysis of methylparaben and propylparaben in zebrafish
- 2019
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 671, s. 129-139
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Tidskriftsartikel (refereegranskat)abstract
- Parabens are widely used as preservatives in different commercial items including food, cosmetics and pharmaceuticals, and their wide use has resulted in accumulation in the environment. Parabens have been shown to have negative effects on animals as well as human health. In this study, we carried out a comprehensive study to determine the adverse effects associated with propylparaben (PP) and methylparaben (MP) on early developmental stages of zebrafish. Mortality, hatching, developmental abnormalities and gene expression profiles were investigated in embryos exposed to both compounds. The semi-static exposure conditions showed that both MP (>= 100 mu M) and PP (>= 10 mu M) are toxic to the embryos in a concentration-dependent manner and lead to developmental abnormality. Malformations such as spinal defects, pericardial edema, and pigmentation defects were observed following both MP and PP treatments. Hatching delay, mortality and developmental abnormality data indicate that PP is more toxic than MP. For gene expression analysis, 1 and 10 mu M doses of MP and PP were analyzed. Genes from physiological pathways including stress response, cell cycle and DNA damage, inflammation, fatty acid metabolism and endocrine functions were affected by MP and PP. The gene expression profiles show that parabens cause toxicity by inducing oxidative stress, DNA double-strand breaks, apoptosis as well as by altering fatty acid metabolism. Altered expression of androgen receptor (ar) and estrogen receptor 2 alpha (esr2a) indicates an antiandrogenic and estrogenic activity of parabens in zebrafish. Overall, the present study provides considerable information on the negative effects of MP and PP using physiological endpoints and motivates further studies to explore the molecular mechanism of the toxicity associated with parabens.
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| 2. |
- Bereketoglu, Ceyhun, et al.
(författare)
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Plasticizers : negative impacts on the thyroid hormone system
- 2022
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Ingår i: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 29:26, s. 38912-38927
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Forskningsöversikt (refereegranskat)abstract
- This review aims to understand the impacts of plasticizers on the thyroid system of animals and humans. The thyroid gland is one of the earliest endocrine glands that appear during embryogenesis. The thyroid gland synthesizes thyroid hormones (TH), triiodothyronine (T3), and thyroxine (T4) that are important in the regulation of body homeostasis. TH plays critical roles in regulating different physiological functions, including metabolism, cell growth, circadian rhythm, and nervous system development. Alteration in thyroid function can lead to different medical problems. In recent years, thyroid-related medical problems have increased and this could be due to rising environmental pollutants. Plasticizers are one such group of a pollutant that impacts thyroid function. Plasticizers are man-made chemicals used in a wide range of products, such as children's toys, food packaging items, building materials, medical devices, cosmetics, and ink. The increased use of plasticizers has resulted in their detection in the environment, animals, and humans. Studies indicated that plasticizers could alter thyroid function in both animals and humans at different levels. Several studies demonstrated a positive and/or negative correlation between plasticizers and serum T4 and T3 levels. Plasticizers could also change the expression of various TH-related genes and proteins, including thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), and transporters. Histological analyses demonstrated thyroid follicular cell hypertrophy and hyperplasia in response to several plasticizers. In conclusion, plasticizers could disrupt TH homeostasis and the mechanisms of toxicity could be diverse.
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| 3. |
- Bereketoglu, Ceyhun, et al.
(författare)
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The brominated flame retardants TBECH and DPTE alter prostate growth, histology and gene expression patterns in the mouse
- 2021
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 43-55
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Tidskriftsartikel (refereegranskat)abstract
- The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). In vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers α and β, a 1:1 mixture of γ and δ, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated (C) mice were used to study the androgenic effects of TBECHαβ and TBECHγδ while the antagonistic effects of DPTE were studied in non-castrated (NC) mice. We observed that testosterone and TBECHγδ increased body and prostate weights while TBECHαβ affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECHγδ group comparable to those in testosterone group while alterations in the TBECHαβ group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECHγδ reversed several of these changes. Testosterone and TBECHγδ also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECHγδ and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function.
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| 4. |
- Bereketoglu, Ceyhun, et al.
(författare)
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Transcriptomic analysis of nonylphenol effect on Saccharomyces cerevisiae
- 2021
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Ingår i: PeerJ. - : PeerJ Inc.. - 2167-8359. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Nonylphenol (NP) is a bioaccumulative environmental estrogen that is widely used as a nonionic surfactant. We have previously examined short-term effects of NP on yeast cells using microarray technology. In the present study, we investigated the adaptive response of Saccharomyces cerevisiae BY4742 cells to NP exposure by analyzing genome-wide transcriptional profiles using RNA-sequencing. We used 2 mg/L NP concentration for 40 days of exposure. Gene expression analysis showed that a total of 948 genes were differentially expressed. Of these, 834 genes were downregulated, while 114 genes were significantly upregulated. GO enrichment analysis revealed that 369 GO terms were significantly affected by NP exposure. Further analysis showed that many of the differentially expressed genes were associated with oxidative phosphorylation, iron and copper acquisition, autophagy, pleiotropic drug resistance and cell cycle progression related processes such as DNA and mismatch repair, chromosome segregation, spindle checkpoint activity, and kinetochore organization. Overall, these results provide considerable information and a comprehensive understanding of the adaptive response to NP exposure at the gene expression level.
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| 5. |
- Pradhan, Ajay, 1983-, et al.
(författare)
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The food preservative ethoxyquin impairs zebrafish development, behavior and alters gene expression profile
- 2020
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Ingår i: Food and Chemical Toxicology. - : Elsevier. - 0278-6915 .- 1873-6351. ; 135
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigated the detrimental effects of ethoxyquin (EQ) on zebrafish embryonic development using different endpoints including lethality, malformations, locomotion and gene expression. EQ is primarily used as a preservative in animal feed and it has been shown to have negative impacts on different laboratory animals. However, studies on the adverse effects of EQ in aquatic animals are still limited. In this study, zebrafish eggs were exposed to different concentrations of EQ ranging from 1 to 100 μM for six days. In the 100 μM treated groups 95 and 100% mortality was observed at 24 and 48 h, respectively. Delayed development, decreased pigmentation and pericardial edema were observed in larvae. Behavioral analysis of larvae demonstrated a distinct locomotive pattern in response to EQ both in light and dark indicating a possible developmental neurotoxicity and deficits in locomotion. The expression levels of genes involved in several physiological pathways including stress response, cell cycle and DNA damage were altered by EQ. Our results demonstrate that EQ could cause developmental and physiological toxicity to aquatic organisms. Hence, its toxic effect should be further analyzed and its use and levels in the environment must be monitored carefully.
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| 6. |
- Saad, Noha, et al.
(författare)
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Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae
- 2021
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Plasticizers are commonly used in different consumer goods and personal care products to provide flexibility, durability and elasticity to polymers. Due to their reported toxicity, the use of several plasticizers, including phthalates has been regulated and/or banned from the market. Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) is an alternative plasticizer that was introduced to replace toxic plasticizers. Increasing global demand and lack of toxicity data and safety assessment of DINCH have raised the concern to human and animal health. Hence, in the present study, we investigated the adverse effects of DINCH (at concentrations ranging from 0.01 to 10 μM) in early developmental stages of zebrafish using different endpoints such as hatching rate, developmental abnormalities, lipid content, behavior analysis and gene expression. We found that DINCH caused hatching delay in a dose-dependent manner and altered the expression of genes involved in stress response. Lipid staining using Oil Red O stain showed a slight lipid accumulation around the yolk, brain, eye and neck with increasing concentration. Genes associated with lipid transport such as fatty acid synthesis, β-oxidation, elongation, lipid transport were significantly altered by DINCH. Genes involved in cholesterol biosynthesis and homeostasis were also affected by DINCH indicating possible developmental neurotoxicity. Behavioral analysis of larvae demonstrated a distinct locomotor activity upon exposure to DINCH. The present data shows that DINCH could induce physiological and metabolic toxicity to aquatic organisms. Hence, further analyses and environmental monitoring of DINCH should be conducted to determine its safety and toxicity levels.
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| 7. |
- Serçinoğlu, Onur, et al.
(författare)
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In silico and in vitro assessment of androgen receptor antagonists
- 2021
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Ingår i: Computational biology and chemistry (Print). - : Elsevier. - 1476-9271 .- 1476-928X. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing concern for male reproductive health as studies suggest that there is a sharp increase in prostate cancer and other fertility related problems. Apart from lifestyle, pollutants are also known to negatively affect the reproductive system. In addition to many other compounds that have been shown to alter androgen signaling, several environmental pollutants are known to disrupt androgen signaling via binding to androgen receptor (AR) or indirectly affecting the androgen synthesis. We analyzed here the molecular mechanism of the interaction between the human AR Ligand Binding Domain (hAR-LBD) and two environmental pollutants, linuron (a herbicide) and procymidone (a pesticide), and compared with the steroid agonist dihydrotestosterone (DHT) and well-known hAR antagonists bicalutamide and enzalutamide. Using molecular docking and dynamics simulations, we showed that the co-activator interaction site of the hAR-LBD is disrupted in different ways by different ligands. Binding free energies of the ligands were also ordered in increasing order as follows: linuron, procymidone, DHT, bicalutamide, and enzalutamide. These data were confirmed by in vitro assays. Reporter assay with MDA-kb2 cells showed that linuron, procymidone, bicalutamide and enzalutamide can inhibit androgen mediated activation of luciferase activity. Gene expression analysis further showed that these compounds can inhibit the expression of prostate specific antigen (PSA) and microseminoprotein beta (MSMB) in prostate cell line LNCaP. Comparative analysis showed that procymidone is more potent than linuron in inhibiting AR activity. Furthermore, procymidone at 10 μM dose showed equivalent and higher activity to AR inhibitor enzalutamide and bicalutamide respectively.
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| 8. |
- Zhai, Gang, et al.
(författare)
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Sex-specific differences in zebrafish brains
- 2022
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Ingår i: Biology of Sex Differences. - : BioMed Central (BMC). - 2042-6410. ; 13:1
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Forskningsöversikt (refereegranskat)abstract
- In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying sex-specific neurological diseases. Male and female brains display subtle differences at the cellular level which may be important in driving sex-specific signaling. Sex differences in the brain have been observed in humans as well as in non-human species. However, the molecular mechanisms of brain sex differentiation remain unclear. The classical model of brain sex differentiation suggests that the steroid hormones derived from the gonads are the primary determinants in establishing male and female neural networks. Recent studies indicate that the developing brain shows sex-specific differences in gene expression prior to gonadal hormone action. Hence, genetic differences may also be responsible for differentiating the brain into male and female types. Understanding the signaling mechanisms involved in brain sex differentiation could help further elucidate the sex-specific incidences of certain neurological diseases. The zebrafish model could be appropriate for enhancing our understanding of brain sex differentiation and the signaling involved in neurological diseases. Zebrafish brains show sex-specific differences at the hormonal level, and recent advances in RNA sequencing have highlighted critical sex-specific differences at the transcript level. The differences are also evident at the cellular and metabolite levels, which could be important in organizing sex-specific neuronal signaling. Furthermore, in addition to having one ortholog for 70% of the human gene, zebrafish also shares brain structural similarities with other higher eukaryotes, including mammals. Hence, deciphering brain sex differentiation in zebrafish will help further enhance the diagnostic and pharmacological intervention of neurological diseases.
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