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Event: 1068

Key Event Title

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

Endometrial squamous metaplasia, Increase

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
Endometrial squamous metaplasia, Increase
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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
squamous epithelial cell

Organ 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
Organ term
endometrium epithelium

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
Metaplasia Squamous cell increased
Metaplasia endometrium epithelium 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
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
Rattus norvegicus Rattus norvegicus High NCBI
Mus musculus Mus musculus High NCBI
Homo sapiens Homo sapiens High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult High
Juvenile Moderate

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

A process in which non-squamous epithelial cells transform into a squamous epithelial phenotype.  This occurs in endometrial epithelial tissue and is a protective adaptation since the stratified squamous cell structure is more resilient to physical and chemical stress than columnar or cuboidal epithelium.  The metaplastic change can be characterized in a number of overlapping ways:

  1. Keratinizing - In this type, your cells make too much keratin (a protein) as they move from one epithelial layer to the next. In healthy squamous cells, this protein helps form tissue, hair, skin and nails. Keratin also makes up the lining of organs and glands (clevelandclinic).
  2. Nonkeratinizing - Your cells don’t accumulate large amounts of protein (keratinization) (clevelandclinic).
  3. Atypical - Squamous cells associated with high-grade squamous intraepithelial lesions (Quddus et al., 2001).
  4. Immature/Mature -  Where immature metaplasia refers to early stages when the new squamous epithelium is not yet fully differentiated and mature refers to well-differentiated, stratified squamous epithelium.

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

Directly:

  • Histopathological examination via tissue biopsy followed by fixation, embedding, sectioning, and staining.
  • Cytological analysis via collecting of exfoliated cells, e.g., smear.

Indirectly:

  • Immunohistohemistry via tissue staining wiht antibodies specific to epithelial markers.

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 squamous metaplasia is well documented humans, rats, and mice (McLachlan et al., 1980; Fluhmann 1954; Sherwood et al., 1997; Kitchen-Goosen 2023).

Lifestage Applicability

Endometrial squamous metaplasia is most commonly studied as a pathological condition, occuring in response chronic inflammation or other stress conditions.  Because of this, it's mostly measured in adults.  Non-pathological squamous metaplasia has been documented during puberty (Hwang et al., 2009).

Sex Applicability

Endometrial squamous metaplasia 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
Fluhmann, C. F. (1954). Comparative studies of squamous metaplasia of the cervix uteri and endometrium. American Journal of Obstetrics and Gynecology, 68(6), 1447-1463.

https://my.clevelandclinic.org/health/diseases/23307-squamous-metaplasia 

Hwang, L. Y., Ma, Y., Benningfield, S. M., Clayton, L., Hanson, E. N., Jay, J., ... & Moscicki, A. B. (2009). Factors that influence the rate of epithelial maturation in the cervix in healthy young women. Journal of Adolescent Health, 44(2), 103-110

Kitchen-Goosen, S. M., Schumacher, H., Good, J., Patterson, A. L., Boguslawski, E. A., West, R. A., ... & Alberts, A. S. (2023). Endometrial hyperplasia with loss of APC in a novel population of Lyz2-expressing mouse endometrial epithelial cells. Carcinogenesis, 44(1), 54-64.
 

McLachlan, J. A., Newbold, R. R., & Bullock, B. C. (1980). Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Research, 40(11), 3988-3999.

Sherwood, J. B., Carlson, J. A., Gold, M. A., Chou, T. Y., Isacson, C., & Talerman, A. (1997). Squamous metaplasia of the endometrium associated with HPV 6 and 11. Gynecologic oncology, 66(1), 141-145.
 
Quddus, M. R., Sung, C. J., Steinhoff, M. M., Lauchlan, S. C., Singer, D. B., & Hutchinson, M. L. (2001). Atypical squamous metaplastic cells: reproducibility, outcome, and diagnostic features on ThinPrep Pap test. Cancer Cytopathology, 93(1), 16-22.