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Aop: 195

AOP Title

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

Short name:

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5-HTT leading to population increase

Graphical Representation

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Click to download graphical representation template

Authors

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Kellie Fay

Point of Contact

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Kellie Fay   (email point of contact)

Contributors

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  • Kellie Fay

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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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

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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.


Background (optional)

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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.


Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 619 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)
2 KE 626 Increased, serotonin (5-HT) Increased, serotonin (5-HT)
3 KE 1161 Increased, oocyte maturation Increased, oocyte maturation
4 KE 1255 induced spawning induced spawning
5 KE 1142 Increased, valve movement Increased, valve movement
6 KE 1163 Increased, Reproductive Success Increased, Reproductive Success
7 KE 621 Increase, cilia movement Increase, cilia movement
8 AO 1164 Increased, Population Increased, Population

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Increased, serotonin (5-HT) leads to Increased, oocyte maturation adjacent
Increased, Reproductive Success leads to Increased, Population adjacent
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, serotonin (5-HT) adjacent
Increased, serotonin (5-HT) leads to Increased, valve movement adjacent
Increased, oocyte maturation leads to induced spawning adjacent
Increased, valve movement leads to induced spawning adjacent
induced spawning leads to Increased, Reproductive Success adjacent
Increase, cilia movement leads to induced spawning adjacent
Increased, serotonin (5-HT) leads to Increase, cilia movement adjacent
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increase, cilia movement non-adjacent
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, oocyte maturation non-adjacent

Network View

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Stressors

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Name Evidence Term
Fluoxetine
Fluvoxamine

Life Stage Applicability

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Taxonomic Applicability

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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

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Overall Assessment of the AOP

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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

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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

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Evidence Assessment

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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.

 


Quantitative Understanding

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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)

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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

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