Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver
Glyphosate is a component of commonly used herbicides for controlling weeds in crops, gardens and municipal parks. There is increasing awareness that glyphosate-based herbicides, in addition to acting on plants, may also exert toxicity in wildlife and humans. In this study, male and female adult zeb...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2724 |
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| author | Christian Giommi Claudia Ladisa Oliana Carnevali Francesca Maradonna Hamid R. Habibi |
| author_facet | Christian Giommi Claudia Ladisa Oliana Carnevali Francesca Maradonna Hamid R. Habibi |
| author_sort | Christian Giommi |
| collection | DOAJ |
| description | Glyphosate is a component of commonly used herbicides for controlling weeds in crops, gardens and municipal parks. There is increasing awareness that glyphosate-based herbicides, in addition to acting on plants, may also exert toxicity in wildlife and humans. In this study, male and female adult zebrafish were exposed to 700 µg/L of glyphosate (GLY), for 28 days. We used the metabolomic approach and UHPLC-ESI-MS to analyze liver samples to investigate the adverse effects of glyphosate on hepatic metabolism. The impact of GLY was found to be sex-specific. In female, GLY exposure affected purine metabolism by decreasing the levels of AMP, GMP and inosinic acid, consequently increasing uric acid levels with respect to the control (CTRL). Exposure to GLY also caused a decrease of UMP levels in the pyrimidine metabolism pathway. In male, GLY exposure decreased the aminoadipic acid within the lysine degradation pathway. Transcript analysis of genes involved in stress response, oxidative stress and the immune system were also performed. Results demonstrated an increased stress response in both sexes, as suggested by higher <i>nr3c1</i> expression. However, the <i>hsp70.2</i> transcript level was increased in female but decreased in male. The results demonstrated reduced <i>sod1</i>, <i>sod2</i>, and <i>gpx1a</i> in male following exposure to GLY, indicating an impaired oxidative stress response. At the same time, an increase in the <i>cat</i> transcript level in female was observed. mRNA levels of the pro-inflammatory interleukins <i>litaf</i> and <i>cxcl8b.1</i> were increased in female. Taken together, the results provide evidence of disrupted nucleotide hepatic metabolism, increased stress inflammatory response in female and disruption of oxidative stress response in male. |
| first_indexed | 2024-03-09T20:37:17Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:37:17Z |
| publishDate | 2022-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc6585115ee14049b5b9f3021d42dbf22023-11-23T23:08:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01235272410.3390/ijms23052724Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish LiverChristian Giommi0Claudia Ladisa1Oliana Carnevali2Francesca Maradonna3Hamid R. Habibi4Dipartimento Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, ItalyDepartment of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, CanadaDipartimento Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, ItalyDipartimento Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, ItalyDepartment of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, CanadaGlyphosate is a component of commonly used herbicides for controlling weeds in crops, gardens and municipal parks. There is increasing awareness that glyphosate-based herbicides, in addition to acting on plants, may also exert toxicity in wildlife and humans. In this study, male and female adult zebrafish were exposed to 700 µg/L of glyphosate (GLY), for 28 days. We used the metabolomic approach and UHPLC-ESI-MS to analyze liver samples to investigate the adverse effects of glyphosate on hepatic metabolism. The impact of GLY was found to be sex-specific. In female, GLY exposure affected purine metabolism by decreasing the levels of AMP, GMP and inosinic acid, consequently increasing uric acid levels with respect to the control (CTRL). Exposure to GLY also caused a decrease of UMP levels in the pyrimidine metabolism pathway. In male, GLY exposure decreased the aminoadipic acid within the lysine degradation pathway. Transcript analysis of genes involved in stress response, oxidative stress and the immune system were also performed. Results demonstrated an increased stress response in both sexes, as suggested by higher <i>nr3c1</i> expression. However, the <i>hsp70.2</i> transcript level was increased in female but decreased in male. The results demonstrated reduced <i>sod1</i>, <i>sod2</i>, and <i>gpx1a</i> in male following exposure to GLY, indicating an impaired oxidative stress response. At the same time, an increase in the <i>cat</i> transcript level in female was observed. mRNA levels of the pro-inflammatory interleukins <i>litaf</i> and <i>cxcl8b.1</i> were increased in female. Taken together, the results provide evidence of disrupted nucleotide hepatic metabolism, increased stress inflammatory response in female and disruption of oxidative stress response in male.https://www.mdpi.com/1422-0067/23/5/2724<i>Danio rerio</i>metabolomicliverglyphosateRoundup<sup>®</sup>purine metabolism |
| spellingShingle | Christian Giommi Claudia Ladisa Oliana Carnevali Francesca Maradonna Hamid R. Habibi Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver International Journal of Molecular Sciences <i>Danio rerio</i> metabolomic liver glyphosate Roundup<sup>®</sup> purine metabolism |
| title | Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver |
| title_full | Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver |
| title_fullStr | Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver |
| title_full_unstemmed | Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver |
| title_short | Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver |
| title_sort | metabolomic and transcript analysis revealed a sex specific effect of glyphosate in zebrafish liver |
| topic | <i>Danio rerio</i> metabolomic liver glyphosate Roundup<sup>®</sup> purine metabolism |
| url | https://www.mdpi.com/1422-0067/23/5/2724 |
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