{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:31:14Z","timestamp":1786987874055,"version":"build-2736575974"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373625"],"award-info":[{"award-number":["82373625"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2023YFF1104103"],"award-info":[{"award-number":["2023YFF1104103"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ecotoxicology and Environmental Safety"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.ecoenv.2025.119305","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:06:58Z","timestamp":1761653218000},"page":"119305","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Phthalates exposure as a risk factor for gestational diabetes mellitus: Integrated evidence from epidemiological and human liver organoids studies"],"prefix":"10.1016","volume":"306","author":[{"given":"Huihui","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhishen","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoying","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-338X","authenticated-orcid":false,"given":"Hui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ecoenv.2025.119305_bib1","unstructured":"Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles. (2022). (A. f. T. S. a. D. R. (US), Ed.). Agency for Toxic Substances and Disease Registry (US)."},{"issue":"12","key":"10.1016\/j.ecoenv.2025.119305_bib2","doi-asserted-by":"crossref","first-page":"33555","DOI":"10.1007\/s11356-022-24454-y","article-title":"Effects of exposure to phthalate during early pregnancy on gestational diabetes mellitus: a nested case-control study with propensity score matching","volume":"30","author":"Chen","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"issue":"3","key":"10.1016\/j.ecoenv.2025.119305_bib3","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cmet.2023.02.003","article-title":"The global burden of metabolic disease: Data from 2000 to 2019","volume":"35","author":"Chew","year":"2023","journal-title":"Cell Metab."},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00204-017-2094-7","article-title":"The PPAR\u03b1-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions","volume":"92","author":"Corton","year":"2018","journal-title":"Arch. Toxicol."},{"issue":"2","key":"10.1016\/j.ecoenv.2025.119305_bib5","article-title":"Low-grade metabolic acidosis as a driver of insulin resistance","volume":"8","author":"DiNicolantonio","year":"2021","journal-title":"Open Heart"},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib6","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1186\/s12889-022-13965-5","article-title":"Environmental health influences in pregnancy and risk of gestational diabetes mellitus: a systematic review","volume":"22","author":"Eberle","year":"2022","journal-title":"BMC Public Health"},{"issue":"2","key":"10.1016\/j.ecoenv.2025.119305_bib7","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3390\/nu12020525","article-title":"Bisphenol A and phthalates in diet: an emerging link with pregnancy complications","volume":"12","author":"Filardi","year":"2020","journal-title":"Nutrients"},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/toxsci\/kfab068","article-title":"Species differences between mouse and human ppar\u03b1 in modulating the hepatocarcinogenic effects of perinatal exposure to a high-affinity human PPAR\u03b1 agonist in mice","volume":"183","author":"Foreman","year":"2021","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.ecoenv.2025.119305_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2022.155439","article-title":"Urinary phthalate metabolite concentrations and personal care product use during pregnancy - Results of a pilot study","volume":"835","author":"Fruh","year":"2022","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.ecoenv.2025.119305_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2021.106677","article-title":"Effects of single and combined gestational phthalate exposure on blood pressure, blood glucose and gestational weight gain: A longitudinal analysis","volume":"155","author":"Gao","year":"2021","journal-title":"Environ. Int"},{"key":"10.1016\/j.ecoenv.2025.119305_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.envres.2025.121186","article-title":"Association between phthalate exposure and metabolic dysfunction-associated steatotic liver disease (MASLD) - systematic literature review","volume":"273","author":"Gogola","year":"2025","journal-title":"Environ. Res"},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41574-018-0096-z","article-title":"The role of hypoxia-inducible factors in metabolic diseases","volume":"15","author":"Gonzalez","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib13","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1038\/s41467-024-48550-4","article-title":"Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth","volume":"15","author":"Hendriks","year":"2024","journal-title":"Nat. Commun."},{"issue":"11","key":"10.1016\/j.ecoenv.2025.119305_bib14","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/s41587-023-01680-4","article-title":"Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis","volume":"41","author":"Hendriks","year":"2023","journal-title":"Nat. Biotechnol."},{"issue":"10448","key":"10.1016\/j.ecoenv.2025.119305_bib15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0140-6736(24)00827-4","article-title":"Pathophysiology from preconception, during pregnancy, and beyond","volume":"404","author":"Hivert","year":"2024","journal-title":"Lancet"},{"issue":"36","key":"10.1016\/j.ecoenv.2025.119305_bib16","doi-asserted-by":"crossref","first-page":"13408","DOI":"10.1021\/acs.est.3c04492","article-title":"Target exposome for characterizing early gestational exposure to contaminants of emerging concern and association with gestational diabetes mellitus","volume":"57","author":"Huang","year":"2023","journal-title":"Environ. Sci. Technol."},{"issue":"7436","key":"10.1016\/j.ecoenv.2025.119305_bib17","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature11826","article-title":"In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration","volume":"494","author":"Huch","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.ecoenv.2025.119305_bib18","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-025-08861-y","article-title":"Generation of human adult hepatocyte organoids with metabolic functions","author":"Igarashi","year":"2025","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib19","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-94343-w","article-title":"Gene expression analysis method integration and co-expression module detection applied to rare glucide metabolism disorders using ExpHunterSuite","volume":"11","author":"Jabato","year":"2021","journal-title":"Sci. Rep."},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12940-018-0399-5","article-title":"Trimester-specific phthalate concentrations and glucose levels among women from a fertility clinic","volume":"17","author":"James-Todd","year":"2018","journal-title":"Environ. Health"},{"key":"10.1016\/j.ecoenv.2025.119305_bib21","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.envint.2016.09.009","article-title":"Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors","volume":"96","author":"James-Todd","year":"2016","journal-title":"Environ. Int"},{"key":"10.1016\/j.ecoenv.2025.119305_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2022.107099","article-title":"Urinary phthalate and DINCH metabolite concentrations and gradations of maternal glucose intolerance","volume":"161","author":"James-Todd","year":"2022","journal-title":"Environ. Int"},{"issue":"8","key":"10.1016\/j.ecoenv.2025.119305_bib23","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S2213-8587(20)30129-7","article-title":"Endocrine-disrupting chemicals: implications for human health","volume":"8","author":"Kahn","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"5","key":"10.1016\/j.ecoenv.2025.119305_bib24","article-title":"Identification and prioritisation for risk assessment of phthalates, structurally similar substances and replacement substances potentially used as plasticisers in materials and articles intended to come into contact with food","volume":"20","author":"Lambr\u00e9","year":"2022","journal-title":"Efsa J."},{"issue":"9","key":"10.1016\/j.ecoenv.2025.119305_bib25","doi-asserted-by":"crossref","first-page":"13965","DOI":"10.1007\/s11356-024-32030-9","article-title":"Role of sleep in asthenospermia induced by di (2-ethyl-hexyl) phthalate","volume":"31","author":"Li","year":"2024","journal-title":"Environ. Sci. Pollut. Res Int"},{"key":"10.1016\/j.ecoenv.2025.119305_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2021.112988","article-title":"Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver","volume":"228","author":"Li","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"issue":"4","key":"10.1016\/j.ecoenv.2025.119305_bib27","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2337\/db21-0535","article-title":"Lactate is a key mediator that links obesity to insulin resistance via modulating cytokine production from adipose tissue","volume":"71","author":"Lin","year":"2022","journal-title":"Diabetes"},{"issue":"6","key":"10.1016\/j.ecoenv.2025.119305_bib28","doi-asserted-by":"crossref","first-page":"746","DOI":"10.3390\/metabo13060746","article-title":"The relationship between phthalates and diabetes: a review","volume":"13","author":"Mariana","year":"2023","journal-title":"Metabolites"},{"issue":"13","key":"10.1016\/j.ecoenv.2025.119305_bib29","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.3390\/ijms20133343","article-title":"Unhealthy levels of phthalates and Bisphenol A in Mexican pregnant women with gestational diabetes and its association to altered expression of miRNAs involved with metabolic disease","volume":"20","author":"Mart\u00ednez-Ibarra","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41572-019-0098-8","article-title":"Gestational diabetes mellitus","volume":"5","author":"McIntyre","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib31","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1210\/clinem\/dgae709","article-title":"Gestational diabetes: an update 60 years After O'Sullivan and Mahan","volume":"110","author":"McIntyre","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"Pt 1","key":"10.1016\/j.ecoenv.2025.119305_bib32","article-title":"Associations of urinary biomarkers of phthalates, phenols, parabens, and organophosphate esters with glycemic traits in pregnancy: The Healthy Start Study","volume":"262","author":"Peng","year":"2024","journal-title":"Environ. Res."},{"issue":"10","key":"10.1016\/j.ecoenv.2025.119305_bib33","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrendo.2017.80","article-title":"Regulation of hepatic glucose metabolism in health and disease","volume":"13","author":"Petersen","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"issue":"3","key":"10.1016\/j.ecoenv.2025.119305_bib34","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ijheh.2015.01.005","article-title":"Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy","volume":"218","author":"Robledo","year":"2015","journal-title":"Int. J. Hyg. Environ. Health"},{"issue":"2","key":"10.1016\/j.ecoenv.2025.119305_bib35","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.mrrev.2011.12.004","article-title":"Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate","volume":"750","author":"Rusyn","year":"2012","journal-title":"Mutat. Res"},{"issue":"5","key":"10.1016\/j.ecoenv.2025.119305_bib36","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1080\/10408440600779065","article-title":"Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver","volume":"36","author":"Rusyn","year":"2006","journal-title":"Crit. Rev. Toxicol."},{"issue":"6","key":"10.1016\/j.ecoenv.2025.119305_bib37","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.ecoenv.2025.119305_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2022.107279","article-title":"Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPAR\u03b3 activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes","volume":"164","author":"Schaffert","year":"2022","journal-title":"Environ. Int."},{"key":"10.1016\/j.ecoenv.2025.119305_bib39","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.envint.2018.12.021","article-title":"Maternal urinary phthalate metabolites in relation to gestational diabetes and glucose intolerance during pregnancy","volume":"123","author":"Shaffer","year":"2019","journal-title":"Environ. Int."},{"key":"10.1016\/j.ecoenv.2025.119305_bib40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.envint.2015.05.016","article-title":"Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study","volume":"83","author":"Shapiro","year":"2015","journal-title":"Environ. Int."},{"issue":"12","key":"10.1016\/j.ecoenv.2025.119305_bib41","article-title":"Update of the risk assessment of di-butylphthalate (DBP), butyl-benzyl-phthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP), di-isononylphthalate (DINP) and di-isodecylphthalate (DIDP) for use in food contact materials","volume":"17","author":"Silano","year":"2019","journal-title":"Efsa J."},{"issue":"10448","key":"10.1016\/j.ecoenv.2025.119305_bib42","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0140-6736(24)00825-0","article-title":"Epidemiology and management of gestational diabetes","volume":"404","author":"Sweeting","year":"2024","journal-title":"Lancet"},{"issue":"2-3","key":"10.1016\/j.ecoenv.2025.119305_bib43","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.tox.2005.02.002","article-title":"Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor","volume":"210","author":"Takeuchi","year":"2005","journal-title":"Toxicology"},{"issue":"4","key":"10.1016\/j.ecoenv.2025.119305_bib44","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3892\/etm.2022.11217","article-title":"Diabetes mellitus: plasticizers and nanomaterials acting as endocrine-disrupting chemicals (Review)","volume":"23","author":"Tuculina","year":"2022","journal-title":"Exp. Ther. Med"},{"issue":"Pt 3","key":"10.1016\/j.ecoenv.2025.119305_bib45","article-title":"Serum concentrations of phthalate metabolites in pregnant women and their association with gestational diabetes mellitus and blood glucose levels","volume":"857","author":"Wang","year":"2023","journal-title":"Sci. Total Environ."},{"issue":"1","key":"10.1016\/j.ecoenv.2025.119305_bib46","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12940-022-00858-8","article-title":"Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: a systematic review and meta-analysis","volume":"21","author":"Yan","year":"2022","journal-title":"Environ. Health"}],"container-title":["Ecotoxicology and Environmental Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0147651325016501?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0147651325016501?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:22:53Z","timestamp":1773328973000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0147651325016501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":46,"alternative-id":["S0147651325016501"],"URL":"https:\/\/doi.org\/10.1016\/j.ecoenv.2025.119305","relation":{},"ISSN":["0147-6513"],"issn-type":[{"value":"0147-6513","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Phthalates exposure as a risk factor for gestational diabetes mellitus: Integrated evidence from epidemiological and human liver organoids studies","name":"articletitle","label":"Article Title"},{"value":"Ecotoxicology and Environmental Safety","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ecoenv.2025.119305","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"119305"}}