Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy
Abstract The objective of this study was to investigate the hepatotoxic effects and molecular mechanisms underlying di(2-ethylhexyl) phthalate (DEHP)-induced intrahepatic cholestasis of pregnancy (ICP) through a network toxicology approach. Utilizing liver transcriptomics in conjunction with the Gen...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-05489-w |
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| author | Lun Zhang Qianqian Huang Yun Yu Yue Jiang Mengzhen Hou Wenkang Tao Cheng Zhang Jianqing Wang |
| author_facet | Lun Zhang Qianqian Huang Yun Yu Yue Jiang Mengzhen Hou Wenkang Tao Cheng Zhang Jianqing Wang |
| author_sort | Lun Zhang |
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| description | Abstract The objective of this study was to investigate the hepatotoxic effects and molecular mechanisms underlying di(2-ethylhexyl) phthalate (DEHP)-induced intrahepatic cholestasis of pregnancy (ICP) through a network toxicology approach. Utilizing liver transcriptomics in conjunction with the GeneCards, DisGeNET, and OMIM databases, we identified 151 potential targets associated with DEHP-induced ICP. Subsequent analyses employing STRING and cytoscape software revealed five core targets: EGFR, STAT3, JUN, FOS, and HSP90AA1. Functional enrichment analysis via gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways indicated significant involvement in cholesterol synthesis, bile salt secretion, and the MAPK signaling pathway. Molecular docking studies conducted using AutoDock demonstrated strong binding affinities between DEHP and these core targets. In conclusion, this study offers novel insights into the molecular mechanisms of DEHP-induced hepatotoxicity during pregnancy while providing a systematic framework for assessing risks associated with DEHP exposure; thus contributing to the prevention and treatment of ICP. |
| format | Article |
| id | doaj-art-2e0870d37e924c8aa090874987496123 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2e0870d37e924c8aa0908749874961232025-08-20T03:38:15ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-05489-wTranscriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancyLun Zhang0Qianqian Huang1Yun Yu2Yue Jiang3Mengzhen Hou4Wenkang Tao5Cheng Zhang6Jianqing Wang7Department of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Toxicology, School of Public Health, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityAbstract The objective of this study was to investigate the hepatotoxic effects and molecular mechanisms underlying di(2-ethylhexyl) phthalate (DEHP)-induced intrahepatic cholestasis of pregnancy (ICP) through a network toxicology approach. Utilizing liver transcriptomics in conjunction with the GeneCards, DisGeNET, and OMIM databases, we identified 151 potential targets associated with DEHP-induced ICP. Subsequent analyses employing STRING and cytoscape software revealed five core targets: EGFR, STAT3, JUN, FOS, and HSP90AA1. Functional enrichment analysis via gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways indicated significant involvement in cholesterol synthesis, bile salt secretion, and the MAPK signaling pathway. Molecular docking studies conducted using AutoDock demonstrated strong binding affinities between DEHP and these core targets. In conclusion, this study offers novel insights into the molecular mechanisms of DEHP-induced hepatotoxicity during pregnancy while providing a systematic framework for assessing risks associated with DEHP exposure; thus contributing to the prevention and treatment of ICP.https://doi.org/10.1038/s41598-025-05489-wDi-2-ethylhexyl phthalateHepatotoxicityIntrahepatic cholestasis of pregnancyTranscriptomicsNetwork toxicology |
| spellingShingle | Lun Zhang Qianqian Huang Yun Yu Yue Jiang Mengzhen Hou Wenkang Tao Cheng Zhang Jianqing Wang Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy Scientific Reports Di-2-ethylhexyl phthalate Hepatotoxicity Intrahepatic cholestasis of pregnancy Transcriptomics Network toxicology |
| title | Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy |
| title_full | Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy |
| title_fullStr | Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy |
| title_full_unstemmed | Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy |
| title_short | Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy |
| title_sort | transcriptomic and network toxicology approaches reveal potential mechanisms of dehp induced intrahepatic cholestasis during pregnancy |
| topic | Di-2-ethylhexyl phthalate Hepatotoxicity Intrahepatic cholestasis of pregnancy Transcriptomics Network toxicology |
| url | https://doi.org/10.1038/s41598-025-05489-w |
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