{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:56:23Z","timestamp":1790952983795,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972996"],"award-info":[{"award-number":["81972996"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Di(2\u2010ethylhexyl) phthalate (DEHP) could induce thyroid injury but the mechanism was unclear. This study combined in vivo and in vitro experiments to clarify the mechanism. In vivo, the offspring of Sprague Dawley rats were gavaged with different doses of DEHP (5, 50, and 250\u2009mg\/[kg\u22c5d]) from in utero to 12\u2009weeks\u2010old. Transcriptome sequencing was used to detect the mRNA expression profile of the offspring's thyroids. Differentially expressed genes were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In vitro, Nthy\u2010ori 3\u20131 cells were exposed to DEHP's metabolite mono (2\u2010ethylhexyl) phthalate (MEHP) to verify the pathway we found by KEGG analysis. The results indicated that DEHP could disorder the thyroid hormones. Compared with the offspring in control group, the mRNA levels of 656 genes were upregulated in the offspring exposed to 50\u2009mg\/(kg\u22c5d) DEHP. The upregulated genes were enriched in the pathway of \u201cprotein processing in the endoplasmic reticulum (ER).\u201d It indicated that the ER stress might play significant role in the thyroid toxicity induced by DEHP. In vitro, the mitochondrial membrane potential (\u0394\u03a8m) level of cells was decreased while the reactive oxygen species level was increased after MEHP exposure. MEHP increased the intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    level and induced ER stress. After ER stress was inhibited by the 4\u2010phenylbutyric acid, the thyroid toxicity caused by MEHP was alleviated. Taken together, our results indicated that DEHP could induce thyroid toxicity by activating ER stress.\n                  <\/jats:p>","DOI":"10.1002\/tox.23648","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T08:48:55Z","timestamp":1661417335000},"page":"2924-2936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Di(2\u2010ethylhexyl) phthalate induced thyroid toxicity via endoplasmic reticulum stress: In vivo and in vitro study"],"prefix":"10.1002","volume":"37","author":[{"given":"Qi","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyonju","family":"Ri","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health Jilin University  Changchun China"},{"name":"Faculty of Public Health Pyongyang Medical University  Pyongyang North Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health Jilin University  Changchun 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