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Event: 1882

Key Event Title

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

Disrupted meiotic initiation of fetal oogonia of the ovary

Short name

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Oocyte meiosis, disrupted

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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

Organ term

Organ term
ovary sex cord

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

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
Inhibition of ALDH1A leading to reduced fertility	KeyEvent	Cataia Ives (send email)	Under development: Not open for comment. Do not cite	Under Development

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
mouse	Mus musculus	High	NCBI
human	Homo sapiens	High	NCBI
rat	Rattus norvegicus	High	NCBI

Life Stages

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

Life stage	Evidence
Foetal	High
Development	High

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

Oocyte meiosis

Oogonia, the female germ cells, are the precursors for the female oocytes. Primary oocytes are formed in the ovaries during fetal development when oogonia enter into prophase I of meiosis; meiotic entry initiates at around embryonic (E) day 13.5 in mice, E15.5 in rats, and gestational week 10-12 in humans. The entry into meiosis is driven by expression of the key genes Stra8, Meiosin and Rec8 and is followed by expression of meiotic proteins including SYCP3 and γH2AX (Baltus et al, 2006; Bowles et al, 2006; Ishiguro et al, 2020; Kojima et al, 2019; Koubova et al, 2014; Spiller et al, 2017). The crucial role for Stra8 in meiotic entry is conserved from mice to humans (Childs et al, 2011).

Disrupted meiotic entry as Key Event

The initiation of meiosis during fetal life is critical for maintenance of the oocytes throughout development and, eventually, for establishing the oocyte pool, or ‘oocyte reserve’ at birth. Without timely fetal entry into meiosis, the oogonia are depleted, as evidenced in Stra8-null mice (Baltus et al, 2006). The Stra8-null female mice are infertile and display abnormally small ovaries that are devoid of oocytes. For Stra8 to be expressed and, therefore, for meiosis to initiate, the oogonia require direct stimulation by atRA as evidenced in mice (Bowles et al, 2016; Bowles et al, 2006; Feng et al, 2021; Koubova et al, 2006; Spiller et al, 2017; Teletin et al, 2017), and humans (Childs et al, 2011; Le Bouffant et al, 2010).

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

There are no OECD-validated assays for measuring meiotic inhibition.

The expression of meiotic factors, such as STRA8, SYCP3, γH2AX, can be assessed at mRNA and/or protein levels and levels measured using primers/probes and antibodies that are commercially available.

Indirect measurements in animal models can be performed using the Stra8 promoter element driving expression of reporter protein GFP (Feng et al, 2021). This reporter assay can detect the presence (GFP) or absence (GFP negative) of Stra8 promoter activation in a semi-quantitative manner.

Domain of Applicability

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

Fetal oocytes need to enter meiosis prophase I to maintain the oocyte population and establish the oocyte pool. This process in conserver between mice, rats and humans.