This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
Point of Contact
- Tao Zhang
- Shuo Wang
- Ludi Li
- An Zhu
- Qi Wang
- Agnes Aggy
|Author status||OECD status||OECD project||SAAOP status|
|Under Development: Contributions and Comments Welcome|
This AOP was last modified on July 16, 2022 18:37
|Increase, TNF||November 18, 2021 21:37|
|Decrease, GLUT4||November 18, 2021 21:32|
|Decrease, Glucose uptake||November 18, 2021 21:38|
|Abnormal, Glucose homeostasis||November 18, 2021 21:44|
|Gestational diabetes mellitus||November 18, 2021 21:47|
|Increase, TNF leads to Decrease, GLUT4||November 18, 2021 21:56|
|Decrease, GLUT4 leads to Decrease, Glucose uptake||November 18, 2021 21:56|
|Decrease, Glucose uptake leads to Abnormal, Glucose homeostasis||November 18, 2021 21:57|
|Abnormal, Glucose homeostasis leads to GDM||November 18, 2021 21:57|
|Diethylhexyl phthalate||November 18, 2021 21:59|
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.
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).
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.
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.
AOP Development Strategy
Summary of the AOP
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Relationships Between Two Key Events (Including MIEs and AOs)
|Increase, TNF leads to Decrease, GLUT4||adjacent||High||Not Specified|
|Decrease, GLUT4 leads to Decrease, Glucose uptake||adjacent||High||Not Specified|
|Decrease, Glucose uptake leads to Abnormal, Glucose homeostasis||adjacent||High||Not Specified|
|Abnormal, Glucose homeostasis leads to GDM||adjacent||High||Not Specified|
Life Stage Applicability