Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish
Abstract Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides i...
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| Veröffentlicht in: | Toxicological sciences 2023-05, Vol.193 (2), p.119-130 |
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| creator | Thrikawala, Savini Mesmar, Fahmi Bhattacharya, Beas Muhsen, Maram Mukhopadhyay, Srijita Flores, Sara Upadhyay, Sanat Vergara, Leoncio Gustafsson, Jan-Åke Williams, Cecilia Bondesson, Maria |
| description | Abstract
Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers. |
| doi_str_mv | 10.1093/toxsci/kfad031 |
| format | Article |
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Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.</description><identifier>ISSN: 1096-6080</identifier><identifier>ISSN: 1096-0929</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfad031</identifier><identifier>PMID: 36951524</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>adipocytes ; Adipogenesis ; adverse effects ; Animals ; Antifungal Agents ; embryo malformations ; Female ; Fungicides, Industrial - metabolism ; Fungicides, Industrial - toxicity ; Humans ; skeleton ; Triazoles - metabolism ; Triazoles - toxicity ; Zebrafish - metabolism</subject><ispartof>Toxicological sciences, 2023-05, Vol.193 (2), p.119-130</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-cd12c3007c533209193bac1a6a1b78fdf4d042f52b38d36a4189552151941b463</citedby><cites>FETCH-LOGICAL-c405t-cd12c3007c533209193bac1a6a1b78fdf4d042f52b38d36a4189552151941b463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36951524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-331493$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:152439863$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Thrikawala, Savini</creatorcontrib><creatorcontrib>Mesmar, Fahmi</creatorcontrib><creatorcontrib>Bhattacharya, Beas</creatorcontrib><creatorcontrib>Muhsen, Maram</creatorcontrib><creatorcontrib>Mukhopadhyay, Srijita</creatorcontrib><creatorcontrib>Flores, Sara</creatorcontrib><creatorcontrib>Upadhyay, Sanat</creatorcontrib><creatorcontrib>Vergara, Leoncio</creatorcontrib><creatorcontrib>Gustafsson, Jan-Åke</creatorcontrib><creatorcontrib>Williams, Cecilia</creatorcontrib><creatorcontrib>Bondesson, Maria</creatorcontrib><title>Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Abstract
Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.</description><subject>adipocytes</subject><subject>Adipogenesis</subject><subject>adverse effects</subject><subject>Animals</subject><subject>Antifungal Agents</subject><subject>embryo malformations</subject><subject>Female</subject><subject>Fungicides, Industrial - metabolism</subject><subject>Fungicides, Industrial - toxicity</subject><subject>Humans</subject><subject>skeleton</subject><subject>Triazoles - metabolism</subject><subject>Triazoles - toxicity</subject><subject>Zebrafish - metabolism</subject><issn>1096-6080</issn><issn>1096-0929</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS1ERT_gyhHlCIe04_hj42NVoCBV6qGFq-XYk63ZbBw8iYD-9aRK2CM9zdOb3zyN9Bh7y-GcgxEXY_pNPl7sWhdA8BfsZHZ1CaYyL1etoYZjdkr0A4BzDeYVOxbaKK4qecLu7nN0j6nDop36bfQxIBWxD5PHwoU4pC32SJEK14ci45CRqEg0Ymo6R-NhHfviEZvs2kgPr9lR6zrCN-s8Y98-f7q_-lLe3F5_vbq8Kb0ENZY-8MoLgI1XQlRguBGN89xpx5tN3YZWBpBVq6pG1EFoJ3ltlKq44kbyRmpxxsoll37hMDV2yHHv8h-bXLSrtZsVWim12dT_5T_G75c25a3djQ9WCC6NmPn3Cz_k9HNCGu0-kseucz2miWy1MQAKav30yvmC-pyIMraHcA72qSi7FGXXouaDd2v21OwxHPB_zczAhwVI0_Bc2F-lgaCg</recordid><startdate>20230531</startdate><enddate>20230531</enddate><creator>Thrikawala, Savini</creator><creator>Mesmar, Fahmi</creator><creator>Bhattacharya, Beas</creator><creator>Muhsen, Maram</creator><creator>Mukhopadhyay, Srijita</creator><creator>Flores, Sara</creator><creator>Upadhyay, Sanat</creator><creator>Vergara, Leoncio</creator><creator>Gustafsson, Jan-Åke</creator><creator>Williams, Cecilia</creator><creator>Bondesson, Maria</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8V</scope></search><sort><creationdate>20230531</creationdate><title>Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish</title><author>Thrikawala, Savini ; Mesmar, Fahmi ; Bhattacharya, Beas ; Muhsen, Maram ; Mukhopadhyay, Srijita ; Flores, Sara ; Upadhyay, Sanat ; Vergara, Leoncio ; Gustafsson, Jan-Åke ; Williams, Cecilia ; Bondesson, Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-cd12c3007c533209193bac1a6a1b78fdf4d042f52b38d36a4189552151941b463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>adipocytes</topic><topic>Adipogenesis</topic><topic>adverse effects</topic><topic>Animals</topic><topic>Antifungal Agents</topic><topic>embryo malformations</topic><topic>Female</topic><topic>Fungicides, Industrial - metabolism</topic><topic>Fungicides, Industrial - toxicity</topic><topic>Humans</topic><topic>skeleton</topic><topic>Triazoles - metabolism</topic><topic>Triazoles - toxicity</topic><topic>Zebrafish - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thrikawala, Savini</creatorcontrib><creatorcontrib>Mesmar, Fahmi</creatorcontrib><creatorcontrib>Bhattacharya, Beas</creatorcontrib><creatorcontrib>Muhsen, Maram</creatorcontrib><creatorcontrib>Mukhopadhyay, Srijita</creatorcontrib><creatorcontrib>Flores, Sara</creatorcontrib><creatorcontrib>Upadhyay, Sanat</creatorcontrib><creatorcontrib>Vergara, Leoncio</creatorcontrib><creatorcontrib>Gustafsson, Jan-Åke</creatorcontrib><creatorcontrib>Williams, Cecilia</creatorcontrib><creatorcontrib>Bondesson, Maria</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Kungliga Tekniska Högskolan</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thrikawala, Savini</au><au>Mesmar, Fahmi</au><au>Bhattacharya, Beas</au><au>Muhsen, Maram</au><au>Mukhopadhyay, Srijita</au><au>Flores, Sara</au><au>Upadhyay, Sanat</au><au>Vergara, Leoncio</au><au>Gustafsson, Jan-Åke</au><au>Williams, Cecilia</au><au>Bondesson, Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2023-05-31</date><risdate>2023</risdate><volume>193</volume><issue>2</issue><spage>119</spage><epage>130</epage><pages>119-130</pages><issn>1096-6080</issn><issn>1096-0929</issn><eissn>1096-0929</eissn><abstract>Abstract
Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>36951524</pmid><doi>10.1093/toxsci/kfad031</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | adipocytes Adipogenesis adverse effects Animals Antifungal Agents embryo malformations Female Fungicides, Industrial - metabolism Fungicides, Industrial - toxicity Humans skeleton Triazoles - metabolism Triazoles - toxicity Zebrafish - metabolism |
| title | Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish |
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