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Mapping DEHP to the adverse outcome pathway network for human female reproductive toxicity.
| Content Provider | Europe PMC |
|---|---|
| Author | Pogrmic-Majkic, Kristina Samardzija Nenadov, Dragana Tesic, Biljana Fa Nedeljkovic, Svetlana Kokai, Dunja Stanic, Bojana Andric, Nebojsa |
| Abstract | Adverse outcome pathways (AOPs) and AOP networks are tools for mechanistic presentation of toxicological effects across different levels of biological organization. These tools are used to better understand how chemicals impact human health. In this study, a four-step workflow was used to derive the AOP network of human female reproductive toxicity (HFRT-AOP) from five AOPs available in the AOP-Wiki and ten AOPs obtained from the literature. Standard network analysis identified key events (KEs) that are point of convergence and divergence, upstream and downstream KEs, and bottlenecks across the network. To map di-(2-ethylhexyl) phthalate (DEHP) to the HFRT-AOP network, we extracted DEHP target genes and proteins from the Comparative Toxicogenomic and the CompTox Chemicals Dashboard databases. Enriched GO terms analysis was used to identify relevant biological processes in the ovary that are DEHP targets, whereas screening of scientific literature was performed manually and automatically using AOP-helpFinder. We combined this information to map DEHP to HFRT-AOP network to provide insight on the KEs and system-level perturbations caused by this endocrine disruptor and the emergent paths. This approach can enable better understanding of the toxic mechanism of DEHP-induced human female reproductive toxicity and reveal potential novel DEHP female reproductive targets for experimental studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00204-022-03333-y. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9352620&blobtype=pdf |
| ISSN | 03405761 |
| Journal | Archives of Toxicology [Arch Toxicol] |
| Volume Number | 96 |
| DOI | 10.1007/s00204-022-03333-y |
| PubMed Central reference number | PMC9352620 |
| Issue Number | 10 |
| PubMed reference number | 35790550 |
| e-ISSN | 14320738 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2022-07-05 |
| Publisher Place | Berlin/Heidelberg |
| Access Restriction | Open |
| Rights License | Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022 |
| Subject Keyword | Adverse outcome pathway (AOP) AOP network Female reproductive toxicity DEHP |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Medicine Toxicology |
