This AOP is licensed under a Creative Commons Attribution 4.0 International License.
5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
- Kellie Fay
|Author status||OECD status||OECD project||SAAOP status|
|Under Development: Contributions and Comments Welcome||1.29||Under Development|
This AOP was last modified on February 07, 2020 14:58
|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|
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.
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
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
|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)
Life Stage Applicability
|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|
Overall Assessment of the AOP
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
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
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.
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)
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.