Diethylhexyl phthalate 2021-11-18T21:59:34 2021-11-18T21:59:34 WCS_9606 common toxicological species human Increase, TNF Molecular AOPWiki 2021-11-18T21:37:13 2021-11-18T21:37:13 Decrease, GLUT4 Cellular AOPWiki 2021-11-18T21:32:12 2021-11-18T21:32:12 Decrease, Glucose uptake Cellular AOPWiki 2021-11-18T21:38:38 2021-11-18T21:38:38 Abnormal, Glucose homeostasis Organ AOPWiki 2021-11-18T21:44:03 2021-11-18T21:44:03 GDM Individual AOPWiki 2021-11-18T21:47:40 2021-11-18T21:47:40 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ea72e770> AOPWiki 2021-11-18T21:56:18 2021-11-18T21:56:18 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ea7b7390> AOPWiki 2021-11-18T21:56:36 2021-11-18T21:56:36 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ea7f8c00> AOPWiki 2021-11-18T21:57:01 2021-11-18T21:57:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ea844da8> AOPWiki 2021-11-18T21:57:19 2021-11-18T21:57:19 Increased TNF leading to GDM Agnes Aggy <p>Qi Wang, Ph.D, Professor<br /> Department of Toxicology, School of Public Health, Peking University, Beijing, China<br /> E-mail:&nbsp;<a href="mailto:wangqi@bjmu.edu.cn" rel="noopener" target="_blank">wangqi@bjmu.edu.cn</a></p> BY-SA 2.0 <p style="text-align:justify"><span style="font-family:Arial,Helvetica,sans-serif"><span style="font-size:14px">Some epidemiologic studies have found an association between exposure to environmental endocrine disruptors (EDCs) and gestational diabetes mellitus (GDM). There is considerable uncertainty on the effects of EDCs&nbsp;exposure to GDM, which may be decreased if its underlying mechanism becomes clearer.&nbsp;This project aims to construct an AOP of GDM for supporting the investigation of the mechanism between environmental chemicals and GDM.<span style="color:black"> </span></span></span></p> <p style="text-align:justify"><span style="font-family:Arial,Helvetica,sans-serif"><span style="font-size:14px"><span style="color:black">We chose diethylhexyl phthalate (DEHP), an endocrine disruptor ubiquitous in the environment, as a case study, and developed a preliminary AOP of GDM using a network-based approach. In this AOP, increased tumor necrosis factor (TNF) was identified as the MIE, and three KEs including decreased glucose transporter type 4 (GLUT4) (subcellular KE), decreased glucose uptake (cellular KE), and unbalanced glucose homeostasis (system KE) were selected to connect increased TNF and GDM (AO).</span></span></span></p> <p style="text-align:justify"><span style="font-family:Arial,Helvetica,sans-serif"><span style="font-size:14px"><span style="color:black">The weight of evidence (WoE) of overall AOP was assessed based on the biological plausibility, empirical support, and evidence supporting essentiality of the KEs and KERs according to the OECD handbook of AOP. As a result, both the biological plausibility and empirical support were rated as &ldquo;High&rdquo;, indicating high confidence in this AOP. </span></span></span></p> <p style="text-align:justify"><span style="font-family:Arial,Helvetica,sans-serif"><span style="font-size:14px"><span style="color:black">This preliminary AOP has the potential to predict the connections between environmental chemicals and GDM, prioritizing the chemical&#39;s subsequent molecular mechanism studies. Further efforts will be focused on identifying quantitative relationships of KERs and incorporating other typical chemicals for external validation to increase the confidence of this AOP.</span></span></span></p> adjacent Not Specified High adjacent Not Specified High adjacent Not Specified High adjacent Not Specified High High Female High Pregnancy High High AOPWiki 2021-11-18T20:27:15 2023-09-25T16:27:10