The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies
Background: This study aimed to assess the exposure level and risk of Di-2-ethylhexyl Phthalate (DEHP) among adults in Jilin Province, China, clarify the impact of DEHP on human thyroid function, and to explore the role of estrogen receptors (ERs)-Notch signaling pathway in the effect of DEHP metabo...
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| Formato: | Artigo |
| Idioma: | English |
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Elsevier
2024-01-01
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| Colecção: | Ecotoxicology and Environmental Safety |
| Assuntos: | |
| Acesso em linha: | http://www.sciencedirect.com/science/article/pii/S0147651323012319 |
| _version_ | 1827609629263134720 |
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| author | Xueting Zhang Yuezhu Zhang Xin Feng Haotang Zhao Hui Ye Xiaoqi Fang Jianwei Cui Wen Qi Lin Ye |
| author_facet | Xueting Zhang Yuezhu Zhang Xin Feng Haotang Zhao Hui Ye Xiaoqi Fang Jianwei Cui Wen Qi Lin Ye |
| author_sort | Xueting Zhang |
| collection | DOAJ |
| description | Background: This study aimed to assess the exposure level and risk of Di-2-ethylhexyl Phthalate (DEHP) among adults in Jilin Province, China, clarify the impact of DEHP on human thyroid function, and to explore the role of estrogen receptors (ERs)-Notch signaling pathway in the effect of DEHP metabolites on thyroid hormones based on population data and in vitro experiments. Methods: 312 adults participated in this study. Urinary DEHP metabolites were determined by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). Two pharmacokinetic models were used to evaluate the estimated daily intake (EDI) and hazard quotient (HQ) of the adults. Multiple linear regression and mediating effect models were used to evaluate the target associations. In cell experiments, thyroid follicular epithelial (Nthy-ori3–1) cells were exposed to mono (2-ethylhexyl) phthalate (MEHP) for testing. The inhibitions of ERα and Notch pathway were conducted by siRNA and Notch pathway inhibitor DAPT. Results: The detection rate of five DEHP metabolites was 97.1∼100.0%. The HQ value of 0.3% of adults was higher than 1. The levels of urinary DEHP metabolites were significantly correlated with thyrotropin (TSH), thyrotropin-releasing hormone (TRH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) and gene (estrogen receptor α (ERα), Notch1, Dll4) levels. The ERα-Notch pathway played a mediating role in the association between DEHP metabolite levels and FT4. The cell results showed, the levels of FT3 and FT4 in cell supernatant decreased after MEHP exposure, and the downward trend was reversed after ERα and notch pathways were inhibited, notch pathway genes also decreased after ERα inhibition. Conclusion: Adults in the Jilin Province of China were widely exposed to DEHP. ERs-Notch pathway played an important role in the effect of DEHP metabolites on thyroid hormones. |
| first_indexed | 2024-03-09T07:36:13Z |
| format | Article |
| id | doaj.art-5bf2e858fda5486091648946feceb8ae |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-09T07:36:13Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-5bf2e858fda5486091648946feceb8ae2023-12-03T05:39:26ZengElsevierEcotoxicology and Environmental Safety0147-65132024-01-01269115727The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studiesXueting Zhang0Yuezhu Zhang1Xin Feng2Haotang Zhao3Hui Ye4Xiaoqi Fang5Jianwei Cui6Wen Qi7Lin Ye8Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaCorrespondence to: 1163 Xin Min Street, Changchun 130000, Jilin, China.; Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaCorrespondence to: 1163 Xin Min Street, Changchun 130000, Jilin, China.; Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130000, Jilin, ChinaBackground: This study aimed to assess the exposure level and risk of Di-2-ethylhexyl Phthalate (DEHP) among adults in Jilin Province, China, clarify the impact of DEHP on human thyroid function, and to explore the role of estrogen receptors (ERs)-Notch signaling pathway in the effect of DEHP metabolites on thyroid hormones based on population data and in vitro experiments. Methods: 312 adults participated in this study. Urinary DEHP metabolites were determined by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). Two pharmacokinetic models were used to evaluate the estimated daily intake (EDI) and hazard quotient (HQ) of the adults. Multiple linear regression and mediating effect models were used to evaluate the target associations. In cell experiments, thyroid follicular epithelial (Nthy-ori3–1) cells were exposed to mono (2-ethylhexyl) phthalate (MEHP) for testing. The inhibitions of ERα and Notch pathway were conducted by siRNA and Notch pathway inhibitor DAPT. Results: The detection rate of five DEHP metabolites was 97.1∼100.0%. The HQ value of 0.3% of adults was higher than 1. The levels of urinary DEHP metabolites were significantly correlated with thyrotropin (TSH), thyrotropin-releasing hormone (TRH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) and gene (estrogen receptor α (ERα), Notch1, Dll4) levels. The ERα-Notch pathway played a mediating role in the association between DEHP metabolite levels and FT4. The cell results showed, the levels of FT3 and FT4 in cell supernatant decreased after MEHP exposure, and the downward trend was reversed after ERα and notch pathways were inhibited, notch pathway genes also decreased after ERα inhibition. Conclusion: Adults in the Jilin Province of China were widely exposed to DEHP. ERs-Notch pathway played an important role in the effect of DEHP metabolites on thyroid hormones.http://www.sciencedirect.com/science/article/pii/S0147651323012319DEHP metabolitesRisk assessmentEstrogen receptorNotch |
| spellingShingle | Xueting Zhang Yuezhu Zhang Xin Feng Haotang Zhao Hui Ye Xiaoqi Fang Jianwei Cui Wen Qi Lin Ye The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies Ecotoxicology and Environmental Safety DEHP metabolites Risk assessment Estrogen receptor Notch |
| title | The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies |
| title_full | The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies |
| title_fullStr | The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies |
| title_full_unstemmed | The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies |
| title_short | The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies |
| title_sort | role of estrogen receptors ers notch pathway in thyroid toxicity induced by di 2 ethylhexyl phthalate dehp exposure population data and in vitro studies |
| topic | DEHP metabolites Risk assessment Estrogen receptor Notch |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323012319 |
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