Aop: 195

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

5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
5-HTT leading to population increase

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

The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Kellie Fay

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
Kellie Fay   (email point of contact)

Contributors

Users with write access to the AOP page.  Entries in this field are controlled by the Point of Contact. More help
  • Kellie Fay

Status

Provides users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. OECD Status - Tracks the level of review/endorsement the AOP has been subjected to. OECD Project Number - Project number is designated and updated by the OECD. SAAOP Status - Status managed and updated by SAAOP curators. More help
Author status OECD status OECD project SAAOP status
Under Development: Contributions and Comments Welcome 1.29 Under Development
This AOP was last modified on June 04, 2021 14:15

Revision dates for related pages

Page Revision Date/Time
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) September 16, 2017 10:15
Increased, serotonin (5-HT) September 16, 2017 10:15
Increased, oocyte maturation January 17, 2017 00:55
Increased, Population December 03, 2016 16:37
induced spawning January 13, 2017 15:38
Increased, valve movement December 03, 2016 16:37
Increased, Reproductive Success December 03, 2016 16:37
Increase, cilia movement January 13, 2017 16:27
Increased, serotonin (5-HT) leads to Increased, oocyte maturation December 03, 2016 16:38
Increased, Reproductive Success leads to Increased, Population December 03, 2016 16:38
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, serotonin (5-HT) December 03, 2016 16:37
Increased, serotonin (5-HT) leads to Increased, valve movement January 17, 2017 01:02
Increased, oocyte maturation leads to induced spawning January 17, 2017 01:02
Increased, valve movement leads to induced spawning January 13, 2017 15:44
induced spawning leads to Increased, Reproductive Success January 13, 2017 16:47
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increase, cilia movement January 13, 2017 15:43
Increase, cilia movement leads to induced spawning January 13, 2017 15:45
Increased, serotonin (5-HT) leads to Increase, cilia movement January 30, 2017 12:20
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, oocyte maturation January 30, 2017 13:25
Fluoxetine November 29, 2016 18:42
Fluvoxamine November 29, 2016 18:42

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

Increased serotonergic activity resulting from the inhibition of the 5-hydroxytryptamin transporter (5-HTT; SERT; serotonin reuptake transporter) may result in increased population levels of certain mollusks, specifically invasive mussels. Gamete maturation and release are under serotonergic control and several mussel species have been reported to release viable gametes (both sperm and oocytes)upon exposure to serotonin or 5-HTT inhibitors, which increase serotonergic signalling. Given the critically low population levels of many Unionid species and the difficulty in managing several invasive (Dreissenid; e.g., zebra mussel) species, increased reproductive success of these invasive species may result in adverse outcomes at an ecosystem level.

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

This AOP was developed, initially, as a case study in developing an AOP for species with known or suscpected chemical exposures, in "Practical approaches to adverse outcome pathway (AOP) development and weight of evidence evaluation as illustrated by ecotoxicological case studies" by Fay et al. 2017.

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

Summary of the AOP

This section is for information that describes the overall AOP. The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help

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 619 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)
KE 626 Increased, serotonin (5-HT) Increased, serotonin (5-HT)
KE 1161 Increased, oocyte maturation Increased, oocyte maturation
KE 1255 induced spawning induced spawning
KE 1142 Increased, valve movement Increased, valve movement
KE 1163 Increased, Reproductive Success Increased, Reproductive Success
KE 621 Increase, cilia movement Increase, cilia movement
AO 1164 Increased, Population Increased, Population

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

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

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.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. More help
Term Scientific Term Evidence Link
Argopecten irradians Argopecten irradians Low NCBI
Mercenaria mercenaria Mercenaria mercenaria Low NCBI
Arctica islandica Arctica islandica Low NCBI
Spisula solidissima Spisula solidissima Low NCBI
Anodonta cygnea Anodonta cygnea Low NCBI
Dreissena polymorpha Dreissena polymorpha Low NCBI

Sex Applicability

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

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

This aop should be considered highly putative. SSRI effects in mussels have been fairly well documented as a method to increase reproduction in aquaculture settings, but the implications on natural population and potential ecosystem effects are unknown.

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

Bivalve populations which employ a broadcast spawning strategy for reproduction appear to be susceptible, including several 'invasive' species: zebra mussels, dark false mussels, and mediterranean mussels.  Several species of clams and scallops also release viable gametes upon exposure to serotonin reuptake inhibitors or serotonin.

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

Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP. More help

Biological plausibility:  Biological plausibility refers to the structural or funtional relationships between the key events based on our understanding of  'normal biology'. Nerves immunoreactive to serotonin have been identified in the CNS and gonads of scallops and clams (e.g., Natsutani and Nomura, 1986; Masseau et al., 2002; Siniscalchi et al., 2004).  Serotonin-reactive sites are also present on the surfaces of bivalve oocytes and serotonin controls germinal vesicle breakdown and, in at least some species, the progression from prophase to metaphase I (Hirai et al., 1994; Fong et al., 1994; Alvarado-Alvarez et al.,1996).  Thus, the link between antagonising the serotonin reuptake transporter, which results in longer residence time of serotonin in synaptic junctions and increased serotonerigic signalling, and increased spawning and reproductive success is highly plausible.

Dose-response concordance:  While there are abundant studies in many species of bivalves indicating exposure to various serotonin reuptake inhibitors or to serotonin results in spawning in both males and females, there are not many direct comparisons available of the concentrations required to trigger upstream events vs concentrations required to trigger downstream events.

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

Quantitative Understanding

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

Exposure effects are not only concentration-dependent, but also season-dependent (see Ram et al., 1993).  Spawning in males appears to be more sensitive to increased serotonin than in females, at least in fingernail clams, surf clams, dark false mussels and zebra mussles (see table and references).

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

The reproductive sensitivity of many bivalves has been well-sutdied.  For commercially-important species, some aquaculture facilities employ fluoxetine or other SSRIs to promote reproduction.  Potential future applications of this AOP may involve pharmacological control of invasive species.

References

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