In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine
Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Bain, Peter A. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2016transfer abstract |
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| Umfang: |
8 |
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| Übergeordnetes Werk: |
Enthalten in: Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product - Wang, Zhuosen ELSEVIER, 2017, CBP : an international journal, London [u.a.] |
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| Übergeordnetes Werk: |
volume:188 ; year:2016 ; pages:1-8 ; extent:8 |
| Links: |
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| DOI / URN: |
10.1016/j.cbpc.2016.05.007 |
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| 245 | 1 | 0 | |a In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine |
| 264 | 1 | |c 2016transfer abstract | |
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| 520 | |a Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. | ||
| 520 | |a Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. | ||
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| 700 | 1 | |a Jena, J.K. |4 oth | |
| 700 | 1 | |a Kumar, Anu |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Pergamon Press |a Wang, Zhuosen ELSEVIER |t Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product |d 2017 |d CBP : an international journal |g London [u.a.] |w (DE-627)ELV007784783 |
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10.1016/j.cbpc.2016.05.007 doi GBVA2016005000001.pica (DE-627)ELV019121318 (ELSEVIER)S1532-0456(16)30064-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 VZ KARTEN DE-1a fid 38.03 bkl 74.48 bkl 74.41 bkl Bain, Peter A. verfasserin aut In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine 2016transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Basheer, V.S. oth Gregg, Adrienne oth Jena, J.K. oth Kumar, Anu oth Enthalten in Pergamon Press Wang, Zhuosen ELSEVIER Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product 2017 CBP : an international journal London [u.a.] (DE-627)ELV007784783 volume:188 year:2016 pages:1-8 extent:8 https://doi.org/10.1016/j.cbpc.2016.05.007 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-KARTEN SSG-OPC-GGO SSG-OPC-AST SSG-OPC-GEO 38.03 Methoden und Techniken der Geowissenschaften VZ 74.48 Geoinformationssysteme VZ 74.41 Luftaufnahmen Photogrammetrie VZ AR 188 2016 1-8 8 045F 610 |
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10.1016/j.cbpc.2016.05.007 doi GBVA2016005000001.pica (DE-627)ELV019121318 (ELSEVIER)S1532-0456(16)30064-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 VZ KARTEN DE-1a fid 38.03 bkl 74.48 bkl 74.41 bkl Bain, Peter A. verfasserin aut In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine 2016transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Basheer, V.S. oth Gregg, Adrienne oth Jena, J.K. oth Kumar, Anu oth Enthalten in Pergamon Press Wang, Zhuosen ELSEVIER Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product 2017 CBP : an international journal London [u.a.] (DE-627)ELV007784783 volume:188 year:2016 pages:1-8 extent:8 https://doi.org/10.1016/j.cbpc.2016.05.007 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-KARTEN SSG-OPC-GGO SSG-OPC-AST SSG-OPC-GEO 38.03 Methoden und Techniken der Geowissenschaften VZ 74.48 Geoinformationssysteme VZ 74.41 Luftaufnahmen Photogrammetrie VZ AR 188 2016 1-8 8 045F 610 |
| allfields_unstemmed |
10.1016/j.cbpc.2016.05.007 doi GBVA2016005000001.pica (DE-627)ELV019121318 (ELSEVIER)S1532-0456(16)30064-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 VZ KARTEN DE-1a fid 38.03 bkl 74.48 bkl 74.41 bkl Bain, Peter A. verfasserin aut In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine 2016transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Basheer, V.S. oth Gregg, Adrienne oth Jena, J.K. oth Kumar, Anu oth Enthalten in Pergamon Press Wang, Zhuosen ELSEVIER Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product 2017 CBP : an international journal London [u.a.] (DE-627)ELV007784783 volume:188 year:2016 pages:1-8 extent:8 https://doi.org/10.1016/j.cbpc.2016.05.007 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-KARTEN SSG-OPC-GGO SSG-OPC-AST SSG-OPC-GEO 38.03 Methoden und Techniken der Geowissenschaften VZ 74.48 Geoinformationssysteme VZ 74.41 Luftaufnahmen Photogrammetrie VZ AR 188 2016 1-8 8 045F 610 |
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10.1016/j.cbpc.2016.05.007 doi GBVA2016005000001.pica (DE-627)ELV019121318 (ELSEVIER)S1532-0456(16)30064-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 VZ KARTEN DE-1a fid 38.03 bkl 74.48 bkl 74.41 bkl Bain, Peter A. verfasserin aut In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine 2016transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. Basheer, V.S. oth Gregg, Adrienne oth Jena, J.K. oth Kumar, Anu oth Enthalten in Pergamon Press Wang, Zhuosen ELSEVIER Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product 2017 CBP : an international journal London [u.a.] (DE-627)ELV007784783 volume:188 year:2016 pages:1-8 extent:8 https://doi.org/10.1016/j.cbpc.2016.05.007 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-KARTEN SSG-OPC-GGO SSG-OPC-AST SSG-OPC-GEO 38.03 Methoden und Techniken der Geowissenschaften VZ 74.48 Geoinformationssysteme VZ 74.41 Luftaufnahmen Photogrammetrie VZ AR 188 2016 1-8 8 045F 610 |
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In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine |
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Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. |
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Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. |
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Fluoxetine (FLX) is one of numerous pharmaceuticals found in treated municipal wastewater discharged to the environment. In the present study, we investigated the effects of short-term (96h) waterborne FLX exposure (1μg/L or 100μg/L) on the expression of selected genes in brain, liver, and gonads of female Murray-Darling rainbowfish (Melanotaenia fluviatilis), a small-bodied teleost of ecotoxicological relevance in the Australasia region. Plasma 17β-estradiol (E2) levels were also determined. In the brain, no significant changes in mRNA levels were observed for the selected genes. In ovaries, 100μg/L FLX caused a 10-fold downregulation of aromatase A (cyp19a1a) mRNA and a 4-fold upregulation of estrogen receptor α (esr1) mRNA levels. In liver, mRNA levels for vitellogenin A (vtga) and choriogenin L (chgl) were downregulated by 50-fold and 18-fold compared with controls, respectively, in response to 100μg/L FLX. Concentrations of E2 in plasma were significantly lower than controls in response to 100μg/L FLX. This could be attributable to a decrease in estrogen biosynthesis as a result of the observed downregulation of cyp19a1a mRNA. To establish whether the observed changes in gene expression could be explained by the modulation of selected nuclear receptors by FLX, we employed panel of reporter gene assays in agonistic and antagonistic modes. Apart from minor activation of ERα after exposure to high concentrations (5μM), FLX did not activate or inhibit the nuclear receptors tested. Further study is required to determine whether the observed downregulation of ovarian aromatase expression and liver estrogen-regulated genes also occurs at environmentally relevant FLX concentrations over longer exposure periods. |
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In vitro nuclear receptor activity and in vivo gene expression analysis in Murray-Darling rainbowfish (Melanotaenia fluviatilis) after short-term exposure to fluoxetine |
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https://doi.org/10.1016/j.cbpc.2016.05.007 |
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Basheer, V.S. Gregg, Adrienne Jena, J.K. Kumar, Anu |
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