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Event: 1790

Key Event Title

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

Increased, Differentiation to Testis

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
Tissue

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
testis

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
male gonad development	immature gonad	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
Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation	KeyEvent	Kelvin Santana Rodriguez (send email)	Under Development: Contributions and Comments Welcome	WPHA/WNT Endorsed
AR agonism leading to male-biased sex ratio	KeyEvent	Dan Villeneuve (send email)	Open for citation & comment	WPHA/WNT Endorsed

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
Development	Moderate

Sex Applicability

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

Term	Evidence
Male	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

Prior to gonadal sex determination in vertebrates, the developing organism has a primordial bipotential gonad that can be fated to either sex depending on the genetic makeup of the embryo (genetic sex determination) or environmental conditions (environmental sex determination) or a combination of both factors.

During male development, the embryonic stem cells can differentiate to primordial germ cells, which in turn proliferate and differentiate into precursor spermatogonia stem cells. Sertoli cells are the first to differentiate into the different fetal gonad seminiferous cords surrounded by peritubular myoid cells enclosing fetal germ cells. Sertoli cells can also differentiate into Leydig cells. Successively, the interstitial Leydig cells differentiate and produce sex steroids such as testosterone to maintain the testis and control aspects of masculinization including secondary sex characteristics (McLaren 1998; DeFalco and Capel 2009; Trukina et al. 2013).

Although the timing and location of gene expression leading to the morphological development of the testis may differ among vertebrate taxa, the basic molecular machinery and pathways involved are well conserved (Cutting et al. 2013). Similarly, the cell types and basic morphological structure of the testis across vertebrates are well-conserved (McLaren 1998; DeFalco and Capel 2009).

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

Depending upon the size of the test organism and life stage it may be possible to identify the presence of developed testes versus ovaries visually or with low-power magnification without a need for gonad removal, fixation and processing. This would require, of course, experienced personnel well-versed in the biology of the species of interest.

In instances where organisms are small, at early life-stages and/or have poorly differentiated gonads, it will be necessary to employ histological examination by light microscopy to identify nature of the gonad. In all vertebrates, the gonads of phenotypic males in early development have three main differentiating cell types; the gamete forming germ cells (spermatogonia), support cells (Sertoli cells), and hormone-secreting Leydig or interstitial cells (DeFalco and Capel 2009; McLaren 1998).

There are many standardized techniques available for fixation, processing and staining of tissues of concern, including gonads (e.g., Carson and Cappellano 2014). There also are species-specific resources available to aid interpretation of histological images; for example, the National Toxicology Program maintains an on-line Atlas of Non-Neoplastic lesions for a variety of organs, including gonads, in rodents (https://ntp.niehs.nih.gov/nnl/index.htm).

Although there are fewer publicly-accessible resources available for interpretation of histological images in other vertebrate classes, there is often published reference material suitable for this purpose (e.g., Spitsbergen et al. 2009).

Domain of Applicability

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

The primordial bipotential gonad and basic molecular machinery/pathways responsible for differentiation of testis and ovary are well conserved across all vertebrates (Cutting et al. 2013; DeFalco and Capel 2009). Although timing/expression of key genes controlling pathways involved in male versus female gonadal differentiation can vary across taxa (Cutting et al. 2013), actual structural morphology of the testes is similar across vertebrates (DeFalco and Capel 2009; McLaren 1998). Consequentially, this KE is applicable to most vertebrate taxa.

References

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

Carson, F. and C.H. Cappellano. 2014. Histotechnology: A Self-Instructional Text. 4^th Ed., ASCP.

Cutting, A., Chue, J., & Smith, C. A. (2013). Just how conserved is vertebrate sex determination?. Developmental dynamics : an official publication of the American Association of Anatomists, 242(4), 380–387.

DeFalco T, Capel B. Gonad morphogenesis in vertebrates: divergent means to a convergent end. Annu Rev Cell Dev Biol. 2009;25:457-482. doi:10.1146/annurev.cellbio.042308.13350

McLaren A. (1998). Gonad development: assembling the mammalian testis. Current biology : CB, 8(5), R175–R177. https://doi.org/10.1016/s0960-9822(98)70104-6

Spitsbergen JM, Blazer VS, Bowser PR, Cheng KC, Cooper KR, Cooper TK, Frasca Jr S, Groman DB, Harper CM, Lawk JM, Marty GD, Smolowitz RM, Leger J, Wolf DC, Wolf JC. 2009. Finfish and aquatic invertebrate pathology resources for now and the future. Comparative Biochemistry and Physiology 149C, 249-257.

Trukhina, A. V., Lukina, N. A., Wackerow-Kouzova, N. D., & Smirnov, A. F. (2013). The variety of vertebrate mechanisms of sex determination. BioMed research international, 2013, 587460. https://doi.org/10.1155/2013/587460