AOP: 540

Title

A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE. More help

Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production

Short name

A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help

ROS in Fish Ovary Impairs Reproduction

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Handbook Version v2.7

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help

Click to download graphical representation template Explore AOP in a Third Party Tool

Authors

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Kevin V. Brix

EcoTox LLC

Miami, Florida

KevinBrix@EcoTox.onmicrosoft.com

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section. More help

Kevin Brix (email point of contact)

Contributors

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Kevin Brix

Coaches

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OECD Information Table

Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication. More help

OECD Project #	OECD Status	Reviewer's Reports	Journal-format Article	OECD iLibrary Published Version

This AOP was last modified on October 16, 2024 09:30

Revision dates for related pages

Page	Revision Date/Time
Increased, Reactive oxygen species	April 10, 2024 17:33
Oxidative Stress	November 15, 2024 10:33
Apoptosis	February 28, 2024 09:40
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	September 16, 2017 10:14
Reduction, Vitellogenin synthesis in liver	May 27, 2021 01:10
Reduction, Plasma vitellogenin concentrations	September 16, 2017 10:14
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	September 16, 2017 10:14
Reduction, Cumulative fecundity and spawning	March 20, 2017 17:52
Decrease, Population growth rate	January 03, 2023 09:09
Increased, Reactive oxygen species leads to Oxidative Stress	August 02, 2024 15:40
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells leads to Reduction, Vitellogenin synthesis in liver	July 26, 2024 11:12
Oxidative Stress leads to Apoptosis	June 19, 2024 04:24
Apoptosis leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	July 26, 2024 11:15
Reduction, Vitellogenin synthesis in liver leads to Reduction, Plasma vitellogenin concentrations	March 20, 2017 12:58
Reduction, Plasma vitellogenin concentrations leads to Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	March 20, 2017 13:21
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development leads to Reduction, Cumulative fecundity and spawning	March 20, 2017 13:35
Reduction, Cumulative fecundity and spawning leads to Decrease, Population growth rate	March 20, 2017 13:49

Abstract

A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

This AOP describes the linkage between excess reactive oxygen species (ROS) in the fish ovary and reductions in fish fecundity leading to population level impacts. The AOP largely relies on key events (KEs) and key event relationships (KERs) that have been previously described in other AOPs linking reduction in estradiol (E2) synthesis to decreased population growth rates. The novel aspect of this AOP is the development of evidence supporting excess ROS and corresponding oxidative stress in the fish ovary as another molecular initiating event (MIE) and initial KE that can lead to initiation of this pathway.

AOP Development Strategy

Context

Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Contaminant induced generation of excess ROS and subsequent oxidative stress has been measured in fish ovaries after exposure to mutliple different classes of toxicants including pesticides, metals, plasticizers, and nanoplastics. Effects on fish reproductive fecundity has also been demonstrated for these stressors either concurrently or in independent studies. This AOP provides linkage between increased oxidative stress and adverse outcomes related to reduced fecundity in fish which is known to significantly effect fish population demographics.

Strategy

Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components. Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

Most of the KEs and KERs in this AOP have already been well documented in previously developed AOPs. The primary areas needing development are documentation of ROS/oxidative stress specific to fish ovaries and the KERs between oxidative stress and apoptosis specific to granulosa cells in the ovary leading to reduction in estradiol synthesis.

Summary of the AOP

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Events:

Molecular Initiating Events (MIE)

An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help

Key Events (KE)

A measurable event within a specific biological level of organisation. More help

Adverse Outcomes (AO)

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

Type	Event ID	Title	Short name

MIE

1115

Increased, Reactive oxygen species

KE	1392	Oxidative Stress	Oxidative Stress
KE	1262	Apoptosis	Apoptosis
KE	3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE	285	Reduction, Vitellogenin synthesis in liver	Reduction, Vitellogenin synthesis in liver
KE	221	Reduction, Plasma vitellogenin concentrations	Reduction, Plasma vitellogenin concentrations
KE	309	Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development
KE	78	Reduction, Cumulative fecundity and spawning	Reduction, Cumulative fecundity and spawning

360

Decrease, Population growth rate

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page. More help

Title	Adjacency	Evidence	Quantitative Understanding

Increased, Reactive oxygen species leads to Oxidative Stress	adjacent	High	Low
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells leads to Reduction, Vitellogenin synthesis in liver	adjacent	Not Specified	Not Specified
Oxidative Stress leads to Apoptosis	adjacent	Not Specified	Not Specified
Apoptosis leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	adjacent	Not Specified	Not Specified
Reduction, Vitellogenin synthesis in liver leads to Reduction, Plasma vitellogenin concentrations	adjacent	High	Moderate
Reduction, Plasma vitellogenin concentrations leads to Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	adjacent	Moderate	Low
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development leads to Reduction, Cumulative fecundity and spawning	adjacent	Moderate	Moderate
Reduction, Cumulative fecundity and spawning leads to Decrease, Population growth rate	adjacent	Moderate	Moderate

Network View

This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help

Prototypical Stressors

A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented. More help

Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help

Taxonomic Applicability

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Sex Applicability

The sex for which the AOP is known to be applicable. More help

Sex	Evidence
Female	High

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help

Evidence Assessment

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Known Modulating Factors

Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs. More help

Modulating Factor (MF)	Influence or Outcome	KER(s) involved

Quantitative Understanding

Optional field to provide quantitative weight of evidence descriptors. More help

Considerations for Potential Applications of the AOP (optional)

Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. More help

References

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