Diethylhexyl phthalate2021-11-18T21:59:342021-11-18T21:59:34WCS_9606humanIncrease, TNFIncrease, TNFMolecular2021-11-18T21:37:132021-11-18T21:37:13Decrease, GLUT4Decrease, GLUT4Cellular2021-11-18T21:32:122021-11-18T21:32:12Decrease, Glucose uptakeDecrease, Glucose uptakeCellular2021-11-18T21:38:382021-11-18T21:38:38Abnormal, Glucose homeostasisAbnormal, Glucose homeostasisOrgan2021-11-18T21:44:032021-11-18T21:44:03Gestational diabetes mellitusGDMIndividual2021-11-18T21:47:402021-11-18T21:47:40d51e00a5-cf11-4776-9d5c-cfa8c01beef203841b85-dbe3-484f-9e88-6c07f5a14dc62021-11-18T21:56:182021-11-18T21:56:1803841b85-dbe3-484f-9e88-6c07f5a14dc6a445f7b1-230b-4f0f-9c97-06cd9fd0a15e2021-11-18T21:56:362021-11-18T21:56:36a445f7b1-230b-4f0f-9c97-06cd9fd0a15eb035fc3e-65ea-4b33-8141-3010a52c977e2021-11-18T21:57:012021-11-18T21:57:01b035fc3e-65ea-4b33-8141-3010a52c977e6e666cd5-9b96-4f5c-a8bc-558ac31c37d52021-11-18T21:57:192021-11-18T21:57:19Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Increased TNF leading to GDM<p>Qi Wang, Ph.D, Professor<br />
Department of Toxicology, School of Public Health, Peking University, Beijing, China<br />
E-mail: <a href="mailto:wangqi@bjmu.edu.cn" rel="noopener" target="_blank">wangqi@bjmu.edu.cn</a></p>
Under Development: Contributions and Comments Welcome<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 exposure to GDM, which may be decreased if its underlying mechanism becomes clearer. 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 “High”, 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'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>
adjacentNot SpecifiedHighadjacentNot SpecifiedHighadjacentNot SpecifiedHighadjacentNot SpecifiedHighHighFemaleHighPregnancyHighHigh2021-11-18T20:27:152023-04-29T13:02:20