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AOP: 203
Title
5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
Short name
Graphical Representation
Point of Contact
Contributors
- Kellie Fay
- Allie Always
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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1.29 |
This AOP was last modified on May 26, 2024 20:39
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 |
Increased, serotonin (5-HT) | September 16, 2017 10:15 |
Decrease, Population growth rate | January 03, 2023 09:09 |
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 |
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 |
Decreased, Reproductive Success leads to Decrease, Population growth rate | April 06, 2022 13:50 |
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
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).
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 619 | Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) | Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) |
KE | 1142 | Increased, valve movement | Increased, valve movement |
KE | 621 | Increase, cilia movement | Increase, cilia movement |
KE | 1256 | increased mantel display | increased mantel display |
KE | 1257 | Induced parturition | Induced parturition |
KE | 626 | Increased, serotonin (5-HT) | Increased, serotonin (5-HT) |
AO | 1141 | Decreased, Reproductive Success | Decreased, Reproductive Success |
AO | 360 | Decrease, Population growth rate | Decrease, Population growth rate |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
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.