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Event: 2400

Key Event Title

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

Preputial epithelial morphogenesis, disrupted

Short name

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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
epithelial cell

Organ term

Organ term
prepuce

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
external genitalia morphogenesis	prepuce	disrupted

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
AR agonism leads to delayed PPS via reduced FGF expression	KeyEvent	Travis Karschnik (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	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
Embryo	High
Foetal	High
Fetal to Parturition	High
Development	High

Sex Applicability

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

Term	Evidence
Unspecific	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

This state is characterized by a disruption of the normal cellular and tissue processes involved in the formation of the prepuce. These processes include:

Cellular proliferation, survival, adhesion, and differentiation.
Tissue formation, position, and presence/absence.

There are cellular and tissue measurements that take place in the preputial tissue, either the foreskin or clitoral hood. The cell types the measurements take place in are epithelial and mesenchymal cells.

When preputial epithelial morphogenesis occurs normally, the result is the appropriate formation of the prepuce, both inner mucosal and outer cutaneous layers, covering and protecting the glans.

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

Direct evidence with well validated and widely used techniques based on quantitative and qualitative histological measurements.

Hematoxylin and eosin staining
Serial sectioning with stereo microscopy, imaging, morphometric analysis
Ki-67 immunostaining and BrdU or EdU incorporation assays for proliferation
TUNEL and cleaved caspase-3 for apoptosis

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

Preputial epithelial morphogenesis is applicable in mammals, having been demonstrated/measured directly in mice and humans (Liu et al., 2018; Cunha et al., 2020) as well as other rodents. It’s not applicable outside of Mammalia because true preputial structures and the associated morphogenesis are mammal specific.

Lifestage Applicability

This is a developmental process primarily applicable in embryonic and fetal stages during the period of external genital morphogenesis.

Sex Applicability

Preputial morphogenesis occurs in both males and females with male morphogenesis culminating in properly developed and attached foreskin and female morphogenesis culminating in properly developed and attached clitoral hood. Concordantly, the phenotypic outcomes of disruption differ.

References

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

Liu, X., Liu, G., Shen, J., Yue, A., Isaacson, D., Sinclair, A., ... & Baskin, L. (2018). Human glans and preputial development. Differentiation, 103, 86-99.

Cunha, G. R., Sinclair, A., Cao, M., & Baskin, L. S. (2020). Development of the human prepuce and its innervation. Differentiation, 111, 22-40.