API XML

Aop: 203

AOP Title

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5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline

Short name:

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5-HTT leading to population decline

Graphical Representation

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Click to download graphical representation template

Authors

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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 Do not cite 1.29 Under Development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, valve movement December 03, 2016 16:37
Increase, cilia movement January 13, 2017 16:27
increased mantel display January 13, 2017 15:39
Induced parturition January 13, 2017 15:40
Decreased, Reproductive Success December 03, 2016 16:37
Decline, Population December 03, 2016 16:33
Increased, serotonin (5-HT) September 16, 2017 10:15
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, valve movement January 13, 2017 11:18
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increase, cilia movement January 13, 2017 15:43
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to increased mantel display January 13, 2017 15:44
increased mantel display leads to Induced parturition January 13, 2017 15:49
Induced parturition leads to Decreased, Reproductive Success January 13, 2017 15:49
Decreased, Reproductive Success leads to Decline, Population December 03, 2016 16:38
Increased, valve movement leads to Induced parturition January 30, 2017 12:23
Increase, cilia movement leads to Induced parturition January 30, 2017 12:24
Increased, serotonin (5-HT) leads to Increased, valve movement January 17, 2017 01:02
Increased, serotonin (5-HT) leads to Increase, cilia movement January 30, 2017 12:20
Increased, serotonin (5-HT) leads to increased mantel display January 30, 2017 12:25
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, serotonin (5-HT) December 03, 2016 16:37
Fluoxetine November 29, 2016 18:42
sertraline January 13, 2017 12:26
Fluvoxamine November 29, 2016 18:42
norfluoxetine January 13, 2017 12:26

Abstract

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Anti-depressants such as fluoxetine inhibit the reuptake of 5-HT by blocking the 5-HTT, causing an increase in serotonin levels at neural junctions. While movement-related endpoints in molluscs may be highly sensitive to 5-HTT inhibition (see AOP: 197), empirical evidence also supports a putative AO for reproductive health because serotonin is reported to control oocyte maturation, spawning and glochidia release (Ram 1993, Bringolf 2010, Meechonkit 2010,Lazarra 2012). Exposure of native freshwater mussels to fluoxetine induced premature release of glochidia resulting in non-viable larvae (Bringolf 2010). One review of fluoxetine effects in aquatic species noted that concentrations observed to impact the reproductive endpoints of mussels can far exceed environmental exposure levels (Sumpter 2014), and this may be a limitation of several key events depicted in this AOP network. However, recent work to address this concern supports several relevant effects at ng/L concentrations (Peters 2016, Ford 2016).


Background (optional)

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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 1142 Increased, valve movement Increased, valve movement
3 KE 621 Increase, cilia movement Increase, cilia movement
4 KE 1256 increased mantel display increased mantel display
5 KE 1257 Induced parturition Induced parturition
6 KE 626 Increased, serotonin (5-HT) Increased, serotonin (5-HT)
7 AO 1141 Decreased, Reproductive Success Decreased, Reproductive Success
8 AO 361 Decline, Population Decline, Population

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
increased mantel display leads to Induced parturition adjacent
Induced parturition leads to Decreased, Reproductive Success adjacent
Decreased, Reproductive Success leads to Decline, Population adjacent
Increased, valve movement leads to Induced parturition adjacent
Increase, cilia movement leads to Induced parturition adjacent
Increased, serotonin (5-HT) leads to Increased, valve movement adjacent
Increased, serotonin (5-HT) leads to Increase, cilia movement adjacent
Increased, serotonin (5-HT) leads to increased mantel display adjacent
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, serotonin (5-HT) adjacent
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Increased, valve movement non-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 mantel display non-adjacent

Network View

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Stressors

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Name Evidence Term
Fluoxetine Moderate
sertraline
Fluvoxamine
norfluoxetine

Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Juvenile and adult mussels are impacted by components of this pathway. Successfull metamorphosis in wavy-rayed lamp mussel glochidia was increased with exposure to fluoxetine (Hazelton et al, 2014), but the same study observed premature release of glochidia resulting in decreased viability in adults exposed to fluoxetine.  Some key events may be unique to specific bivalve taxa due to different life history strategies (e.g, not all species rely on mantel display or release glochidia in the same manner).  Spawning and gametogenesis effects are sex-specific, but serotonin is reported to induce spawning in both male and female mussels.


Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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