Auflistung nach Autor:in "Fent, Karl"

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ABC transporters and xenobiotic defense systems in early life stages of rainbow trout (Oncorhynchus mykiss)
(Elsevier, 02.03.2016) Kropf, Christian; Segner, Helmut; Fent, Karl
Embryos of oviparous fish, in contrast to (ovo) viviparous species, develop in the aquatic environment, and therefore need solute transport systems at their body surfaces for maintaining internal homeostasis and defending against potentially harmful substances. We hypothesized that solute transporters undergo changes in tissue distribution from the embryo to the larval stage. We therefore studied the mRNA profiles of eight ABC transporters (abcb1a, abcb1b, abcc1, abcc2, abcc3, abcc4, abcc5, abcg2) and three solute carriers (oatp1d, putative oatp2 putative, mate1) in different body regions (head, yolk sac epithelium, abdominal viscera, skin/muscles) of developing rainbow trout. Additionally, we investigated mRNA levels of phase I (cyp1a, cyp3a) and phase II (gstp, putative ugt1, putative ugt2) biotransformation enzymes. The study covered the developmental period from the eleuthero-embryo stage to the first-feeding larval stage (1-20days post-hatch, dph). At 1dph, transcripts of abcc2, abcc4, abcg2, cyp3a, gstp, putative mate1, and putative oatp2 occurred primarily in the yolk sac epithelium, whereas at later stages expression of these genes was predominantly observed in the abdominal viscera. The functional activity of ABC transporters in fish early life stages was assessed by rhodamine B accumulation assays. Finally, we investigated the potential impact of xenobiotics (clotrimazole, clofibric acid) on the ABC and biotransformation systems of trout early life stages. While clofibric acid had no effect, clotrimazole lead to an increased rhodamine B accumulation. The results provide evidence that the transition from the eleuthero-embryo to the larval stage is accompanied by a major alteration in tissue expression of ABC transporters.
01A - Beitrag in wissenschaftlicher Zeitschrift
Activity of binary mixtures of drospirenone with progesterone and 17?-ethinylestradiol in vitro and in vivo
(Elsevier, 22.02.2016) Rossier, Nadine Madeleine; Chew, Geraldine; Zhang, Kun; Riva, Francesco; Fent, Karl
Despite potential exposure of aquatic organisms to mixtures of steroid hormones, very little is known on their joint activity in fish. Drospirenone (DRS) is a new synthetic progestin used in contraceptive pills in combination with 17α-ethinylestradiol (EE2). Here we systematically analyzed effects of DRS in binary mixtures with progesterone (P4) and EE2. First, we determined the in vitro activity of single compounds in recombinant yeast assays that express the human progesterone, androgen, or estrogen receptor, followed by determination of mixture activities of DRS and P4, DRS and EE2, as well as medroxyprogesterone acetate (MPA) and dydrogesterone (DDG). Mixtures of DRS and P4, as well as of DRS and EE2 showed additive progestogenic and androgenic activities. However, DDG and MPA showed non-additive progestogenic and androgenic activities. We then analyzed the in vivo activity of single compounds and mixtures of DRS and P4, as well as DRS and EE2, by assessing transcriptional changes of up to 14 selected target genes in zebrafish embryos at 48h post fertilization (hpf), and in eleuthero-embryos at 96hpf and 144hpf. DRS, P4, and EE2 led to significant transcriptional alteration of genes, including those encoding hormone receptors (pgr, esr1), a steroidogenic enzyme (hsd17b3), and estrogenic markers (vtg1, cyp19b), in particular at 144 hpf. In general, DRS showed stronger transcriptional changes than P4. In mixtures of DRS and P4, they were mainly non-additive (antagonistic interaction). In mixtures of DRS and EE2, transcriptional responses of esr1, vtg1 and cyp19b were dominated by EE2, suggesting an antagonistic interaction or independent action. Equi-effective mixtures of DRS and EE2, based on progesterone receptor transcripts, showed antagonistic interactions. Our data suggest that interactions in mixtures assessed in vitro in recombinant yeast cannot be translated to the in vivo situation. The receptor-based responses did not correspond well to the transcriptional responses in embryos which are much more complex due to the interplay between hormonal pathways, receptor crosstalk, and hormonal feedback loops.
01A - Beitrag in wissenschaftlicher Zeitschrift
Anti-Inflammatory Activity of Cyanobacterial Serine Protease Inhibitors Aeruginosin 828A and Cyanopeptolin 1020 in Human Hepatoma Cell Line Huh7 and Effects in Zebrafish (Danio rerio)
(MDPI, 14.07.2016) Faltermann, Susanne; Hutter, Simon; Christen, Verena; Hettich, Timm; Fent, Karl
Intensive growth of cyanobacteria in freshwater promoted by eutrophication can lead to release of toxic secondary metabolites that may harm aquatic organisms and humans. The serine protease inhibitor aeruginosin 828A was isolated from a microcystin-deficient Planktothrix strain. We assessed potential molecular effects of aeruginosin 828A in comparison to another cyanobacterial serine protease inhibitor, cyanopeptolin 1020, in human hepatoma cell line Huh7, in zebrafish embryos and liver organ cultures. Aeruginosin 828A and cyanopeptolin 1020 promoted anti-inflammatory activity, as indicated by transcriptional down-regulation of interleukin 8 and tumor necrosis factor α in stimulated cells at concentrations of 50 and 100 µmol·L−1 aeruginosin 828A, and 100 µmol·L−1 cyanopeptolin 1020. Aeruginosin 828A induced the expression of CYP1A in Huh7 cells but did not affect enzyme activity. Furthermore, hatched zebrafish embryos and zebrafish liver organ cultures were exposed to aeruginosin 828A. The transcriptional responses were compared to those of cyanopeptolin 1020 and microcystin-LR. Aeruginosin 828A had only minimal effects on endoplasmic reticulum stress. In comparison to cyanopeptolin 1020 our data indicate that transcriptional effects of aeruginosin 828A in zebrafish are very minor. The data further demonstrate that pathways that are influenced by microcystin-LR are not affected by aeruginosin 828A.
01A - Beitrag in wissenschaftlicher Zeitschrift
Are degrading OPV materials still sustainable?
(2015) Zimmermann, Yannick; Brun, Nadja; Hengevoss, Dirk; Corvini, Philippe; Fent, Karl; Hugi, Christoph; Lenz, Markus
06 - Präsentation
Binary mixtures of neonicotinoids show different transcriptional changes than single neonicotinoids in honeybees (Apis mellifera)
(Elsevier, 11.11.2016) Christen, Verena; Bachofer, Sara; Fent, Karl;
Among the many factors responsible for the decline of bee populations are plant protection products such as neonicotinoids. In general, bees are exposed to not only one but mixtures of such chemicals. At environmental realistic concentrations neonicotinoids may display negative effects on the immune system, foraging activity, learning and memory formation of bees. Neonicotinoids induce alterations of gene transcripts such as nicotinic acetylcholine receptor (nAChR) subunits, vitellogenin, genes of the immune system and genes linked to memory formation. While previous studies focused on individual compounds, the effect of neonicotinoid mixtures in bees is poorly known. Here we investigated the effects of neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam as single compounds, and binary mixtures thereof in honeybees. We determined transcriptional changes of nAChR subunits and vitellogenin in the brain of experimentally exposed honeybees after exposure up to 72 h. Exposure concentrations were selected on the basis of lowest effect concentrations of the single compounds. Transcriptional induction of nAChRs and vitellogenin was strongest for thiamethoxam, and weakest for acetamiprid. To a large extent, binary mixtures did not show additive transcriptional inductions but they were less than additive. Our data suggest that the joint transcriptional activity of neonicotinoids cannot be explained by concentration addition. The in vivo effects are not only governed by agonistic interaction with nAChRs alone, but are more complex as a result of interactions with other pathways as well. Further studies are needed to investigate the physiological joint effects of mixtures of neonicotinoids and other plant protection products on bees to better understand their joint effects.
01A - Beitrag in wissenschaftlicher Zeitschrift
Biopesticide spinosad induces transcriptional alterations in genes associated with energy production in honey bees (Apis mellifera) at sublethal concentrations
(Elsevier, 15.10.2019) Christen, Verena; Krebs, Jana; Bünter, Ivan; Fent, Karl
01A - Beitrag in wissenschaftlicher Zeitschrift
Circularity and environmental sustainability of organic and printed electronics
(Jenny Stanford Publishing, 2024) Le Blévennec, Kévin; Hengevoss, Dirk; Zimmermann, Yannick-Serge; Brun, Nadja; Hugi, Christoph; Lenz, Markus; Corvini, Philippe; Fent, Karl; Nisato, Giovanni; Lupo, Donald; Rudolf, Simone
In this chapter, the possible role and impact of organic and printed electronics (OPE) in a transition toward a circular economy and more sustainable society will be discussed. The learning targets are twofold: first, understanding main environmental issues associated with the emerging field of OPE, and second, identifying, through a systemic perspective, the enabling potential of these technologies.
04A - Beitrag Sammelband
Comparative effects of nodularin and microcystin-LR in zebrafish: 1. Uptake by organic anion transporting polypeptide Oatp1d1 (Slco1d1)
(Elsevier, 02/2016) Faltermann, Susanne; Prétôt, René; Pernthaler, Jakob; Fent, Karl
Microcystin-LR (MC-LR) and nodularin are hepatotoxins produced by several cyanobacterial species. Their toxicity is based on active cellular uptake and subsequent inhibition of protein phosphatases PP1/2A, leading to hyperphosphorylation and cell death. To date, uptake of MC-LR and nodularin in fish is poorly understood. Here, we investigated the role of the organic anion transporting polypeptide Oatp1d1 in zebrafish (drOatp1d1, Slco1d1) in cellular uptake in zebrafish. We stably transfected CHO and HEK293 cell lines expressing drOatp1d1. In both transfectants, uptake of MC-LR and nodularin was demonstrated by competitive inhibition of uptake with fluorescent substrate lucifer yellow. Direct uptake of MC-LR was demonstrated by immunostaining, and indirectly by the high cytotoxicity in stable transfectants. By means of a synthesized fluorescent labeled MC-LR derivative, direct uptake was further confirmed in HEK293 cells expressing drOatp1d1. Additionally, uptake and toxicity was investigated in the permanent zebrafish liver cell line ZFL. These cells had only a low relative abundance of drOatp1d1, drOatp2b1 and drOatp1f transcripts, which correlated with the lack of MC-LR induced cytotoxicity and transcriptional changes of genes indicative of endoplasmic reticulum stress, a known effect of this toxin. Our study demonstrates that drOatp1d1 functions as an uptake transporter for both MC-LR and nodularin in zebrafish.
01A - Beitrag in wissenschaftlicher Zeitschrift
Corticosteroid Fludrocortisone Acetate Targets Multiple End Points in Zebrafish (Danio rerio) at Low Concentrations
(Taylor & Francis, 12.09.2016) Zhao, Yanbin; Zhang, Kun; Fent, Karl
Synthetic corticosteroids may pose an environmental risk to fish. Here, we describe multiend point responses of adult zebrafish (8 months old) upon 21-day exposure to a commonly prescribed corticosteroid, fludrocortisone acetate (FLU), at concentrations between 0.006 and 42 μg/L. No remarkable reproductive impacts were observed, while physiological effects, including plasma glucose level and blood leukocyte numbers were significant altered even at 42 ng/L. Ovary parameters and transcriptional analysis of hypothalamic–pituitary–gonadal–liver axis revealed negligible effects. Significant alterations of the circadian rhythm network were observed in the zebrafish brain. Transcripts of several biomarker genes, including per1a and nr1d1, displayed strong transcriptional changes, which occurred at environmental relevant concentrations of 6 and 42 ng/L FLU. Importantly, the development and behavior of F1 embryos were significant changed. Heartbeat, hatching success and swimming behavior of F1 embryos were all increased even at 6 and 42 ng/L. All effects were further confirmed by exposure of eleuthero-embryos. Significant transcriptional changes of biomarker genes involved in gluconeogenesis, immune response and circadian rhythm in eleuthero-embryos confirmed the observations in adult fish. Hatching success, heartbeat, and swimming activity were increased at 81 ng/L and higher, as with F1 embryos. These results provide novel insights into the understanding of potential environmental risks of corticosteroids.
01A - Beitrag in wissenschaftlicher Zeitschrift
Cytotoxicity and molecular effects of biocidal disinfectants (quaternary ammonia, glutaraldehyde, poly(hexamethylene biguanide) hydrochloride PHMB) and their mixtures in vitro and in zebrafish eleuthero-embryos
(Elsevier, 2017) Christen, Verena; Faltermann, Susanne; Fent, Karl; Brun, Nadja
Frequently used biocidal disinfectants, including quaternary ammonium compounds (QAC), glutaraldehyde and poly(hexamethylene biguanide) hydrochloride (PHMB), occur in the aquatic environment but their potential effects in fish are poorly known, in particular when occurring as mixtures. To investigate their joint activity, we assessed the cytotoxicity of three QACs (BAC, barquat and benzalkonium chloride), glutaraldehyde andPHMB by the MTT assay individually, followed by assessing binary and ternary mixtures in zebrafish liver cells (ZFL) and human liver cells (Huh7). We also analysed molecular effects by quantitative PCR in vitro and in zebrafish eleuthero-embryos employing a targeted gene expression approach. QACs displayed strong cytotoxicity in both cell lines with EC50 values in the low μg/ml range, while glutaraldehyde and PHMB were less cytotoxic. Most of the binary and both ternary mixtures showed synergistic activity at all equi-effective concentrations. A mixture containing all five compounds mixed at their no observed effect concentrations showed strong cytotoxicity, suggesting a synergistic interaction. Additionally, we determined transcriptional alterations of target genes related to endoplasmatic reticulum (ER) stress, general stress, inflammatory action and apoptosis. Induction of ER stress genes occurred at non-cytotoxic concentrations of barquat, glutaraldehyde and BAC in ZFL cells. Barquat and BAC induced tumor necrosis factor alpha (tnf-α). Similar transcriptional alterations were found in vivo upon exposure of zebrafish eleuthero-embryos for 120 h. Glutaraldehyde led to induction of ER stress genes and tnf-α, while BAC additionally induced genes indicative of apoptosis, which was also the case with benzalkonium chloride at the highest concentration. We demonstrated strong cytotoxicity of QACs, and synergistic activity of binary, ternary and quintuple mixtures. Barquat and BAC let to induction of ER stress and inflammation in vitro, and BAC and glutaraldehyde at non-toxic concentrations in vivo, while benzalkonium chloride induced expression of tnf-α only.
01A - Beitrag in wissenschaftlicher Zeitschrift
Determination of two progestin metabolites (17a-hydroxypregnanolone and pregnanediol) and different classes of steroids (androgens, estrogens, clorticosteroids, progestins) in rivers and wastewaters by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
(Elsevier, 2018) Fent, Karl; Zhang, Kun
A highly sensitive and robust method was developed for routine analysis of two progestin metabolites, 17α-hydroxypregnanolone (17OH-Δ5P) and pregnanediol (PD), and 31 other natural and synthetic steroids and related metabolites (estrogens, androgens, corticosteroids, progestins) in river water, as well as influents and effluents of municipal wastewater treatment plants (WWTP) using HPLC-MS/MS combined with solid-phase extraction. For the various matrixes considered, the optimized method showed satisfactory performance with recoveries of 70–120% for most of target steroids. The method detection limits (MDLs) ranged from 0.01 to 3 ng/L for river water, 0.02 to 10 ng/L for WWTP effluents, and 0.1 to 40 ng/L for influents with good linearity and reproducibility. The developed method was successfully applied for the analysis of steroids in rivers and WWTP influent and effluents. WWTP influents concentrations of 17OH-Δ5P and PD were 51–256 ng/L and up to 400 ng/L, respectively, along with androstenedione (concentration range: 38–220 ng/L), testosterone (11–26 ng/L), estrone (2.3–37 ng/L), 17β-estradiol (N.D.–8.7 ng/L), 17α-hydroxyprogesterone (N.D.–66 ng/L), medroxyprogesterone acetate (N.D.–5.3 ng/L), and progesterone (2.0–22 ng/L), while only androstenedione (ADD), estrone (E1), and estriol (E3) were detected in effluent with concentrations ranging up to 1.7 ng/L, 0.90 ng/L and 0.8 ng/L, respectively. In river water samples, only ADD and E1 were detected with concentrations up to 1.0 ng/L and 0.91 ng/L. Our procedure represents the first method for analyzing 17OH-Δ5P and PD in environmental samples along with a large series of steroids.
01A - Beitrag in wissenschaftlicher Zeitschrift
Developmental neurotoxicity of different pesticides in PC-12 cells in vitro
(Elsevier, 2017) Christen, Verena; Fent, Karl; Rusconi, Manuel; Crettaz, Pierre
The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor and different concentrations of biocides for 5 days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals.
01A - Beitrag in wissenschaftlicher Zeitschrift
Ecotoxicological Assessment of Solar Cell Leachates
(2015) Fent, Karl; Brun, Nadja; Wehrli, Bernhard
06 - Präsentation
Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17a-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos
(Elsevier, 01/2017) Siegenthaler, Patricia Franziska; Bain, Peter; Riva, Francesco; Fent, Karl
Synthetic progestins act as endocrine disrupters in fish but their risk to the environment is not sufficiently known. Here, we focused on an unexplored antiandrogenic progestin, chlormadinone acetate (CMA), and the antiandrogenic progestin cyproterone acetate (CPA). The aim was to evaluate whether their in vitro interaction with human and rainbowfish (Melanotaenia fluviatilis) sex hormone receptors is similar. Furthermore, we investigated their activity in zebrafish (Danio rerio) eleuthero-embryos. First, we studied agonistic and antagonistic activities of CMA, CPA, and 17α-ethinylestradiol (EE2), in recombinant yeast expressing either the human progesterone (PGR), androgen (AR), or estrogen receptor. The same compounds were also investigated in vitro in a stable transfection cell system expressing rainbowfish nuclear steroid receptors. For human receptors, both progestins exhibited progestogenic, androgenic and antiestrogenic activity with no antiandrogenic or estrogenic activity. In contrast, interactions with rainbowfish receptors showed no progestogenic, but antiandrogenic, antiglucocorticoid, and some antiestrogenic activity. Thus, interaction with and transactivation of human and rainbowfish PGR and AR were distinctly different. Second, we analyzed transcriptional alterations in zebrafish eleuthero‐embryos at 96 and 144 h post fertilization after exposure to CPA, CMA, EE2, and binary mixtures of CMA and CPA with EE2, mimicking the use in oral contraceptives. CMA led to slight down-regulation of the ar transcript, while CPA down-regulated ar and pgr transcripts. EE2 exposure resulted in significant transcriptional alterations of several genes, including esr1, pgr, vtg1, cyp19b, and gonadotropins (fshb, lhb). The mixture activity of CMA and EE2 followed the independent action model, while CPA and EE2 mixtures showed additive action in transcriptional alterations. Third, we analyzed the interactions of binary mixtures of CMA and CPA, and of CMA and EE2 for their joint activity in vitro and in eleuthero-embryos. Both mixtures behaved according to the concentration addition model in their in vitro interaction with human and rainbowfish receptors, often showing antagonism. In zebrafish eleuthero-embryos, binary mixtures of CMA and EE2 showed the same expression patterns as EE2 alone, indicating an independent action in vivo. Our study demonstrates that CMA and CPA interact distinctly with human and rainbowfish receptors, suggesting that activities of these and possibly additional environmental steroids determined with yeast expressing human receptors cannot simply be translated to fish. The lack of agonistic activities of both progestins to rainbowfish PGR and AR is the probable reason for the low activity found in zebrafish eleuthero-embryos.
01A - Beitrag in wissenschaftlicher Zeitschrift
Effects of new generation progestins, including as mixtures and in combination with other classes of steroid hormones, on zebrafish early life stages
(Elsevier, 23.12.2019) Willi, Raphael; Fent, Karl; Schmid, Simon
01A - Beitrag in wissenschaftlicher Zeitschrift
Endocrine disruption and chronic effects of plant protection products in bees: Can we better protect our pollinators?
(Elsevier, 09/2018) Christen, Verena; Kunz, Petra Y.; Fent, Karl
Exposure to plant protection products (PPPs) is one of the causes for the population decline of pollinators. In addition to direct exposure, pollinators are exposed to PPPs by pollen, nectar and honey that often contain residues of multiple PPPs. While in legislation PPPs are regarded mainly for their acute toxicity in bees, other effects such as neurotoxicity, immunotoxicity, behavioural changes, stress responses and chronic effects that may harm different physiologically and ecologically relevant traits are much less or not regarded. Despite the fact that endocrine disruption by PPPs is among key effects weakening survival and thriving of populations, pollinators have been poorly investigated in this regard. Here we summarize known endocrine disruptive effects of PPPs in bees and compare them to other chronic effects. Endocrine disruption in honey bees comprise negative effects on reproductive success of queens and drones and behavioural transition of nurse bees to foragers. Among identified PPPs are insecticides, including neonicotinoids, fipronil, chlorantraniliprole and azadirachtin. So far, there exists no OECD guideline to investigate possible endocrine effects of PPPs. Admittedly, investigation of effects on reproduction success of queens and drones is rarely possible under laboratory conditions. But the behavioural transition of nurse bees to foragers could be a possible endpoint to analyse endocrine effects of PPPs under laboratory conditions. We identified some genes, including vitellogenin, which regulate this transition and which may be used as biomarkers for endocrine disruptive PPPs. We plea for a better implementation of the adverse outcome pathway concept into bee's research and propose a procedure for extending and complementing current assessments, including OECD guidelines, with additional physiological and molecular endpoints. Consequently, assessing potential endocrine disruption in pollinators should receive much more relevance.
01A - Beitrag in wissenschaftlicher Zeitschrift
Environmental aspects of printable and organic electronics (POE)
(Pan Stanford Publishing, 04/2016) Hengevoss, Dirk; Zimmermann, Yannick; Brun, Nadja; Hugi, Christoph; Lenz, Markus; Corvini, Philippe; Fent, Karl; Nisato, Giovanni; Lupo, Donald; Ganz, Simone
04A - Beitrag Sammelband
Environmental chemicals affect circadian rhythms. An underexplored effect influencing health and fitness in animals and humans
(Elsevier, 04/2021) Zheng, Xuehan; Zhang, Kun; Zhao, Yanbin; Fent, Karl
Circadian rhythms control the life of virtually all organisms. They regulate numerous aspects ranging from cellular processes to reproduction and behavior. Besides the light-dark cycle, there are additional environmental factors that regulate the circadian rhythms in animals as well as humans. Here, we outline the circadian rhythm system and considers zebrafish (Danio rerio) as a representative vertebrate organism. We characterize multiple physiological processes, which are affected by circadian rhythm disrupting compounds (circadian disrupters). We focus on and summarize 40 natural and anthropogenic environmental circadian disrupters in fish. They can be divided into six major categories: steroid hormones, metals, pesticides and biocides, polychlorinated biphenyls, neuroactive drugs and other compounds such as cyanobacterial toxins and bisphenol A. Steroid hormones as well as metals are most studied. Especially for progestins and glucocorticoids, circadian dysregulation was demonstrated in zebrafish on the molecular and physiological level, which comprise mainly behavioral alterations. Our review summarizes the current state of knowledge on circadian disrupters, highlights their risks to fish and identifies knowledge gaps in animals and humans. While most studies focus on transcriptional and behavioral alterations, additional effects and consequences are underexplored. Forthcoming studies should explore, which additional environmental circadian disrupters exist. They should clarify the underlying molecular mechanisms and aim to better understand the consequences for physiological processes.
01A - Beitrag in wissenschaftlicher Zeitschrift
Environmental glucocorticoids corticosterone, betamethasone and flumethasone induce more potent physiological than transcriptional effects in zebrafish embryos
(Elsevier, 01.07.2019) Willi, Raffael Alois; Faltermann, Susanne; Hettich, Timm; Fent, Karl
Many glucocorticoids occur in the aquatic environments but their adverse effects to fish are poorly known. Here we investigate effects of the natural glucocorticoid corticosterone and the synthetic glucocorticoids betamethasone and flumethasone in zebrafish embryos. Besides studying the effects of each steroid, we compared effects of natural with synthetic glucocorticoids, used as drugs. Exposure at concentrations of 1 μg/L and higher led to concentration-related decrease in spontaneous muscle contractions at 24 h post fertilization (hpf) and increase in heart rate at 48 hpf. Betamethasone showed a significant increase at 0.11 μg/L in heart rate. Corticosterone also accelerated hatching at 60 hpf at 0.085 μg/L. Transcription of up to 24 genes associated with different pathways showed alterations at 96 and 120 hpf for all glucocorticoids, although with low potency. Corticosterone caused transcriptional induction of interleukin-17, while betamethasone caused transcriptional down-regulation of the androgen receptor, aromatase and hsd11b2, indicating an effect on the sex hormone system. Furthermore, transcripts encoding proteins related to immune system regulation (irg1l, gilz) and fkbp5 were differentially expressed by corticosterone and betamethasone, while flumethasone caused only little effects, mainly alteration of the irg1l transcript. Our study shows that these glucocorticoids caused more potent physiological effects in early embryos than transcriptional alterations in hatched embryos, likely due to increased metabolism in later developmental stages. Thus, these glucocorticoids may be of concern for early stages of fish embryos in contaminated aquatic environments.
01A - Beitrag in wissenschaftlicher Zeitschrift
Environmental Progestins Progesterone and Drospirenone Alter the Circadian Rhythm Network in Zebrafish (Danio rerio)
(American Chemical Society, 2015) Fent, Karl; Castiglioni, Sara; Zhao, Yanbin
01A - Beitrag in wissenschaftlicher Zeitschrift