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Event: 656

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII)

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Decreased COUP-TFII in Leydig cells

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Biological Context

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Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
eukaryotic cell

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
receptor transactivation	COUP transcription factor 2	decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status
Decreased Fetal Testosterone 1	KeyEvent	Cataia Ives (send email)	Under Development: Contributions and Comments Welcome
Decreased Fetal Testosterone 2	KeyEvent	Brendan Ferreri-Hanberry (send email)	Under Development: Contributions and Comments Welcome
Decreased Fetal Testosterone 3	KeyEvent	Arthur Author (send email)	Under Development: Contributions and Comments Welcome
Decreased COUP-TFII in Leydig cells leads to Impaired, Spermatogenesis	KeyEvent	Arthur Author (send email)	Under development: Not open for comment. Do not cite
Decreased COUP-TFII in Leydig cells leads to Hypospadias, increased	KeyEvent	Agnes Aggy (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
mammals	mammals	Moderate	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Development	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII), also known as Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) (Mendoza-Villarroel et al. 2014), is a nuclear receptor involved in various metabolic systems including lipid regulation and steroid synthesis (Qin et al. 2008; van den Driesche et al. 2012; Ashraf et al. 2018). COUP-TFII has been shown to interact with Retinoid X Receptor (RXR) and Glucocorticoid Receptor (GR) (Ashraf et al. 2018). Decrease in COUP-TFII expression has been linked to metabolic and developmental disorders.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

COUP-TFII is measured by changes in gene expression and protein levels. Effects of COUP-TFII on expression of downstream genes can be investigating using metabolomics and RT-qPCR approaches. In addition, targeted ToxCast assays using SeqAPASS evaluations can evaluate gene expression changes from chemical exposure for model species (NCBI Accession Number NP_066285.1 for NR2F2 in Lalone et al. 2018).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Life Stage: Applies to all life stages.

Sex: Applies to both males and females.

Taxonomic: Most representative studies have been done in mammals (humans, lab mice, lab rats); plausible for all vertebrates.

References

List of the literature that was cited for this KE description. More help

Ashraf, U.M., Sanchez, E.R., and Kumarasamy, S. 2019. COUP-TFII Revisited: Its Role in Metabolic Gene Regulation. Steroids 141: 63–69.

LaLone, C.A., Villeneuve, D.L., Doering, J.A., Blackwell, B.R., Transue, T.R., Simmons, C.W., Swintek, J., Degitz, S.J., Williams, A.J., and Ankley, G.T. 2018. Evidence for Cross Species Extrapolation of Mammalian-Based High-Throughput Screening Assay Results. Environmental Science and Technology 52: 13960−13971.

Mendoza-Villarroel, R.E., Robert, N.M., Martin, L.J., Brousseau, C., and Tremblay, J.J. 2014. The Nuclear Receptor NR2F2 Activates Star Expression and Steroidogenesis in Mouse MA-10 and MLTC-1 Leydig Cells. Biology of Reproduction 91(1) Article 26: 1-12.

Qin, J., Tsai, M.-J., and Tsai S.Y. 2008. Essential Roles of COUP-TFII in Leydig Cell Differentiation and Male Fertility. Public Library of Science One 3(9): e3285. van den Driesche, S., Walker, M., McKinnel, C., Scott, HM., Eddie, S.L., Mitchell, R.T., Seckl, J.R., Drake, A.J., Smith, L.B., Anderson, R.A., and Sharpe, R.M. 2012. Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents. Public Library of Science One 7(5): e37064.

NOTE: Italics symbolize edits from John Frisch