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Event: 1515

Key Event Title

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

Spermatocyte depletion

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
	spermatocyte	decreased

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
Histone deacetylase inhibition leading to testicular atrophy	KeyEvent	Brendan Ferreri-Hanberry (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
Rattus norvegicus	Rattus norvegicus	Moderate	NCBI
Mus musculus	Mus musculus	High	NCBI

Life Stages

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

Life stage	Evidence
Adult	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

Spermatocytes are differentiated from spermatogonial stem cells via random proliferation, differentiation, and synchronized mitoses with several stages [Rooij, 2001]. In each step of the spermatogonial differentiation, different molecular mechanisms are activated in the testis [Rooij, 2001; de Kretser et al., 2016]. The stem cell factor (SCF) genes are involved in differentiation into A1 spermatogonia. The expression of cyclin D2 is regulated in the epithelial stage VIII when the aligned spermatogonia differentiate into A1 spermatogonia [Rooij, 2001]. Upon the apoptosis of spermatogonia, overexpression of the apoptosis-inhibiting proteins Bcl-2 and Bcl-xL and deficiency of the apoptosis-inducing protein Bax have been shown to cause an accumulation of spermatogonia in the testis, leading to apoptosis of all cells [Rooij, 2001].

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

Traditional spermatocytes assessment includes sperm count and concentration (haemocytometer, automated image-based system), morphology and motility (microscope, automated image-based system) and viability (for example propidium iodide staining of necrotic cells, TUNEL assay staining apoptotic cells). In addition, there are functional tests such as assays for genetic integrity (e.g. via measurement of DNA fragmentation/integrity -Halosperm kit or reactive oxygen species) and fertilization defects (through various measures of sperm-zona pellucida (ZP) interaction, such as measurement of ZP-receptor binding).

The sperm-containing fluid was squeezed out of the cauda, and suspended in medium containing HEPES buffer and bovine serum albumin, and incubated at 37ºC for 20 min. The number of spermatozoa was determined by a haematocytometer [Zindy et al., 2001].

Testicular sperm counts and daily sperm production were determined by counting the total number of spermatids per testis and divided by the testicular weight to give the results in spermatids per gram of testis [Oishi, 2001].

For the testis cell analysis, fresh testes were dispersed using two-stage enzymatic digestion and incubated in BSA containing collagenase and DNase I [Wade et al., 2006]. The seminiferous tubules were further digested and cells were fixed in ice-cold 70% ethanol [Wade et al., 2006]. Relative proportions of spermatogenic cell populations were assessed in fixed cells using a flow cytometric method [Wade et al., 2006]. The principle of the test is that spermatogenic cells, as they differentiate from normal diploid spermatogonial stem cells through to mature spermatozoa with a highly condensed haploid complement of DNA, progress through various intermediate stages with differing nuclear DNA content and cellular content of mitochondria. Relative proportions of cells in each population were calculated with WinList software [Wade et al., 2006].

Domain of Applicability

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

There are pieces of evidence of spermatocyte depletion in different species.

・Mature sperm counts were decreased and the residual spermatozoa had reduced motility and decreased viability (Mus musculus) [Zindy et al., 2001].

・The sperm counts in the cauda epididymis of rats were significantly decreased (Rattus norvegicus) [Oishi, 2001].

・Spermatocyte death can be induced in Sprague-Dawley rats (Rattus norvegicus) [Wade et al., 2008].

References

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

de Kretser, D.M. et al. (2016), "Endocrinology: Adult and Pediatric (Seventh Edition)", W.B. Saunders, Chapter 136-Spermatogenesis, pages 2325-2353.e9, Editors: J. Larry Jameson, Leslie J De Groot, David M. de Kretser, Linda C. Giudice, Ashley B. Grossman, Shlomo Melmed, John T. Potts, Gordon C. Weir

Oishi, S. (2001), "Effects of butylparaben on the male reproductive system in rats", Toxicol Indust Health 17:31-39

Rooij, D.G. (2001), "Proliferation and differentiation of spermatogonial stem cells", Reproduction 121:347-354

Wade, M.G. et al. (2006), "Testicular toxicity of candidate fuel additive 1,6-dimethoxyhexane: comparison with several similar aliphatic ethers", Toxicol Sci 89:304-313

Wade, M.G. et al. (2008), "Methoxyacetic acid-induced spermatocyte death is associated with histone hyperacetylation in rats", Biol Reprod 78:822-831

Zindy, F. et al. (2001), "Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18Ink4c and p19Ink4d", Mol Cell Biol 21:3244-3255