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Event: 772

Key Event Title

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

Increase, Hyperplasia (glandular epithelial cells of endometrium)

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

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

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
glandular cell of endometrium

Organ term

Organ term
endometrium

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
endometrium hyperplasia	glandular cell of endometrium	increased
hyperplasia	glandular epithelial cell	increased

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	OECD Status
Dopaminergic activity- endometrial carcinoma	KeyEvent	Charles Wood (send email)	Under Development: Contributions and Comments Welcome
Activation of uterine estrogen receptor-alfa, endometrial adenocarcinoma	KeyEvent	Barbara Viviani (send email)	Under development: Not open for comment. Do not cite	Under Review
Early-life ER agonism and endometrial adenosquamous carcinoma via SIX1 expression	KeyEvent	Travis Karschnik (send email)	Under Development: Contributions and Comments Welcome

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	High	NCBI
rodentia	rodentia	High	NCBI

Life Stages

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

Life stage	Evidence
Adult, reproductively mature	High
Adult	High

Sex Applicability

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

Term	Evidence
Female	High

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

Endometrial hyperplasia is a proliferation of endometrial glands characterized by an increase in the gland-to-stroma ration when compared with normal proliferative endometrium.

In 2014 the World Health Organization (WHO) updated their classification system to include two categories (Kurman 2014).

Hyperplasia without atypia – an overgrowth of endometrial cells that still appear relatively normal and are less likely to develop into cancer.
Atypical hyperplasia – an abnormal epithelial cell proliferation that is not extensive enough to be classified as carcinoma in situ. It is considered a non-cancerous, or benign, condition but is also a high-risk lesion for the later development of breast cancer

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

OECD (2007), Test No. 440: Uterotrophic Bioassay in Rodents: A short-term screening test for oestrogenic properties, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264067417-en

Hematoxylin and Eosin staining to visualize the cellular and architectural changes indicative of hyperplasia.
Immunohistochemistry staining by using specific antibodies to identify abnormal or increased levels of certain proteins.
Morphometry to conduct quantitaive analysis of tissue features.

Domain of Applicability

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

Taxonomic Applicability

Endometrial hyperplasia is well established in human gynecology but has also been measured in:

Dogs and Cats (Schlafer & Foster 2016 and Potter et al., 1991)
Chinchilla (Granson et al., 2011)
Pigs (Wood et al., 2020)
Wild canids (Asa et al., 2014)

It plausibly applies to all mammals.

Lifestage Applicability

In humans, endometrial hyperplasia has been shown to occur from reproductive age (19-39) through peri and post-menopausal stages (Takai et al., 2016 and Reed et al., 2009), with incidence in younger women possibly related to symptomatic uterine conditions.

Sex Applicability

Endometrial hyperplasia is a female only condition, as it affects the endometrium, which the lining of the uterus.

References

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

Asa, C. S., Bauman, K. L., Devery, S., Zordan, M., Camilo, G. R., Boutelle, S., & Moresco, A. (2014). Factors associated with uterine endometrial hyperplasia and pyometra in wild canids: implications for fertility. Zoo Biology, 33(1), 8-19.

Granson, H. J., Carr, A. P., Parker, D., & Davies, J. L. (2011). Cystic endometrial hyperplasia and chronic endometritis in a chinchilla. Journal of the American Veterinary Medical Association, 239(2), 233-236.

Kurman, R. J., Carcangiu, M. L., Herrington, C. S., & Young, R. H. (2014). WHO classification of tumours of the female reproductive organs (IARC WHO classification of tumours). World Health Organization, 1-309.

Potter, K., Hancock, D. H., & Gallina, A. M. (1991). Clinical and pathologic features of endometrial hyperplasia, pyometra, and endometritis in cats: 79 cases (1980-1985). Journal of the American veterinary medical association, 198(8), 1427-1431.

Reed, S. D., Newton, K. M., Clinton, W. L., Epplein, M., Garcia, R., Allison, K., ... & Weiss, N. S. (2009). Incidence of endometrial hyperplasia. American journal of obstetrics and gynecology, 200(6), 678-e1.

Schlafer, D. H., & Foster, R. A. (2016). Female genital system. Jubb, Kennedy & Palmer's Pathology of Domestic Animals: Volume 3, 358.

Takai, I. U., Bukar, M., Mayun, A. A., Ugwa, E. A., Audu, B. M., & Abdurrahman, A. (2016). Endometrial hyperplasia: A-2 decade retrospective analysis of histopathological pattern at a university teaching hospital in Northern Nigeria. Sub-Saharan African Journal of Medicine, 3(4), 171-175.

Wood, P., Hall, J. L., McMillan, M., Constantino‐Casas, F., & Hughes, K. (2020). Presence of cystic endometrial hyperplasia and uterine tumours in older pet pigs in the UK. Veterinary Record Case Reports, 8(1), e000924.