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Event: 1616

Key Event Title

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

Malformation, cryptorchidism - maldescended testis

Short name

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Malformation, cryptorchidism

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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
Organ

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

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
animal organ development		abnormal

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
Cyp17A1 inhibition leads to undescended testes in mammals	AdverseOutcome	Bérénice COLLET (send email)	Open for citation & comment
Androgen receptor antagonism and testicular cancer	KeyEvent	Chander K. Negi (send email)	Under development: Not open for comment. Do not cite
Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity	AdverseOutcome	Yue Zhang (send email)	Under development: Not open for comment. Do not cite
Decreased INSL3 leads to Increased, cryptorchidism	AdverseOutcome	John Frisch (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
Vertebrates	Vertebrates	Moderate	NCBI

Life Stages

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

Life stage	Evidence
During development and at adulthood	Moderate

Sex Applicability

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

Term	Evidence
Male	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

Undescended testis is a testicular disorder syndrome known as cryptorchidism. Testis migration is a major event in male fetus development, as it will directly affect his reproductive health.

Cryptorchidism can defined itself as the insertion of the testis in another position than the scrotum. Although the events leading to this pathology occurred during development, cryptorchidism can only be defined after birth though clinical examination as palpation.

Cryptorchidism can be either uni- or bilateral and has been reported to increase in incidence over the decades (Denmark, UK, India…). The maldescended testis will experiment heat stress (37 against 33C outside the body) interfering with testicular physiology and development of germ cells into spermatogonia. Germ cells maturation failure will induce a non-reversible reduction in fertility power of the individual. Cryptorchidism is an established risk factor for infertility and is known to increase the incidence of testicular germ cell tumors (TGCT) ¹²³

Remark:

Cryptorchidism is the first AO of a larger list including raise in testicular cancer and germ cell tumor incidence, as well as reduced fertility due to impairment in germ cells maturation.

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

Cryptorchidism is a birth defect that can be highlighted by a clinical examination. The aim of this palpation is to locate the gonad and determine its lowest position without causing painful traction on the spermatic cord. ⁴

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: Problems first can be observed during development, with adverse outcome manifesting in mature individuals.

Sex: Applies to males.

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

NOTE: Italics symbolize edits from John Frisch

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

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

¹ Hutson J.M., Li R., Southwell B.R., Newgreen D., and Cousinery M. (2015) Regulation of testicular descent. Pediatric Surgery International, 31(4): 317-325. https://doi.org/10.1007/s00383-015-3673-4

² Boisen K.A., Kaleva M., Main K.M., Virtanen H.E., Haavisto A.M., Schmidt I.M., Chellakooty M., Damgaard I.N., Mau C., Reunanen M., Skakkebaek N.E. and Toppari J. (2004) Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet, 17;363(9417):1264-9 https://doi.org/10.1016/S0140-6736(04)15998-9

³ Acerini C.L., Miles H.L., Dunger D.B., Ong K.K. and Hughes I.A. (2009) The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort. Archives of disease in childhood, 94(11):868-72 https://doi.org10.1136/adc.2008.150219

⁴ Hutson J.M., et al. (2015) Cryptorchidism and Hypospadias. Endotexthttps://www.ncbi.nlm.nih.gov/books/NBK279106/