{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:59:16Z","timestamp":1790881156562,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Province science and technology development plan project","award":["20240602089RC"],"award-info":[{"award-number":["20240602089RC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Sulfometuron-methyl (SM), as a sulfonylurea herbicide, is widely used in agricultural production. In recent years, it has also been employed in the control and management of Spartina alterniflora in some coastal areas of China. Its potential risks to aquatic ecosystems have drawn increasing attention. However, the current data on the systematic toxicity assessment of SM in model organisms is still very limited. This study used zebrafish (Danio rerio) as an in vivo model to systematically evaluate the toxic effects of SM on early embryonic development and focused on the mediating mechanism of the Wnt\/\u03b2-catenin signaling pathway in it. Zebrafish embryos were exposed to different concentrations (10, 20, 40 mg\/L) of SM starting from 1.75 hpf until 72 hpf. The results showed that SM significantly increased the embryo mortality rate, decreased the hatching rate, and induced developmental malformations such as shortened body length and yolk sac edema in a concentration-dependent manner. At the mechanism level, SM exposure significantly reduced the number of H3P-positive mitotic active cells in the embryos, suggesting that fewer cells entered mitosis; meanwhile, the activities of superoxide dismutase (SOD) and catalase (CAT) showed compensatory changes, indicating that oxidative stress was induced in the embryos, which may contribute to subsequent cellular damage. qRT-PCR analysis further revealed that SM exposure downregulated the transcriptional levels of cell cycle-related genes (CyclinD1, CDK4, CDK6), while upregulating the expression of apoptosis-related genes (p53, bax, caspase-9, caspase-3), suggesting that cell cycle arrest and the dysregulation of the endogenous apoptotic pathway were activated. Additionally, SM exposure could dysregulate the Wnt\/\u03b2-catenin signaling pathway, specifically manifested as significant upregulation of target genes C-myc and Ctnnb2, and significant downregulation of the negative regulatory factor Axin2. Using the Wnt\/\u03b2-catenin pathway-specific inhibitor IWR-1 for intervention could partially reverse the embryonic developmental retardation phenotypes induced by SM, providing additional evidence for the mediating role of this pathway in the developmental toxicity of SM. In summary, this study systematically elucidates the multi-level molecular mechanism by which SM induces oxidative stress and cell apoptosis through the abnormal dysregulation of the Wnt\/\u03b2-catenin signaling pathway, reduced mitotic activity, and ultimately drives the toxicity of zebrafish embryo development. This provides new experimental evidence and a theoretical basis for the aquatic ecological risk assessment of SM.<\/jats:p>","DOI":"10.3390\/toxics14090835","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:59:41Z","timestamp":1790877581000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sulfometuron-Methyl Disrupts Early Zebrafish Embryonic Development via Wnt\/\u03b2-Catenin Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Xiaomei","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"},{"name":"National Engineering Research Center of Cell Growth Factor Drugs and Protein Preparations (Jilin Center), Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Jinlong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5020-6806","authenticated-orcid":false,"given":"Yongxin","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jun","family":"Zhong","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Shuoqian","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Ziwei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Weidong","family":"Qiang","sequence":"additional","affiliation":[{"name":"College of Medicine, Huanghuai University, Zhumadian 463000, China"},{"name":"Zhumadian Key Laboratory of Zebrafish-Intelligent Pharmaceutical Technology Collaborative Innovation, Zhumadian 463000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Huiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jilin Medical University, Jilin 132013, China"},{"name":"National Engineering Research Center of Cell Growth Factor Drugs and Protein Preparations (Jilin Center), Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24143","DOI":"10.1007\/s11356-018-2481-5","article-title":"Screening effects of metsulfuron-methyl to collembolans and earthworms: The role of adjuvant addition on ecotoxicity","volume":"25","author":"Ramos","year":"2018","journal-title":"Environ. 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