Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment
Pharmaceuticals such as selective serotonin reuptake inhibitors (SSRIs), are increasingly detected in aquatic environments, posing potential risks to non-target organisms, because many of those substances are widely shared neuromodulator. In this study, we investigated the effects of SSRI antidepres...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1536438/full |
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| author | Diana Ilyaskina Yumi Nakadera Yumi Nakadera Marja H. Lamoree Joris M. Koene Pim E. G. Leonards |
| author_facet | Diana Ilyaskina Yumi Nakadera Yumi Nakadera Marja H. Lamoree Joris M. Koene Pim E. G. Leonards |
| author_sort | Diana Ilyaskina |
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| description | Pharmaceuticals such as selective serotonin reuptake inhibitors (SSRIs), are increasingly detected in aquatic environments, posing potential risks to non-target organisms, because many of those substances are widely shared neuromodulator. In this study, we investigated the effects of SSRI antidepressant, namely, fluoxetine, exposure on the freshwater snail L. stagnalis, focusing on egg development, neurochemical pathways, and lipid metabolism. Snails were exposed to a range of 51–434 µg fluoxetine L⁻1 for 7 days, followed by analysis of survival, feeding behaviour, reproduction, and metabolomic changes in the central nervous system (CNS), albumen gland, and eggs. Although no significant effects were observed on survival or fecundity, fluoxetine exposure significantly impaired egg development in a dose-dependent manner, reducing hatching rates with an EC50 of 126 µg fluoxetine L⁻1. Removal of eggs from the contaminated environment partially reversed these developmental effects, suggesting potential recovery if fluoxetine levels decrease. Molecular analysis revealed several neurochemical and lipidomic alterations. In the CNS, elevated levels of catecholamines, phosphatidylcholines (PC), and ceramides were linked to disruptions in neurotransmission, membrane integrity, and impaired embryo development. In the albumen gland, we detected a decrease of key lipid classes, including sphingomyelins and fatty acids, which can be linked with impaired egg quality. Additionally, a decrease in histamine in both the albumen gland and eggs suggested further disruption of egg development, potentially affecting metamorphosis success. Moreover, the dose-dependent increase in choline, along with PC and oxidized PC, indicated oxidative stress and lipid peroxidation in the CNS and exposed eggs of Lymnaea stagnalis. Our findings highlight the benefits of combining behavioral assessments with metabolomic profiling to better understand the mechanistic pathways underlying fluoxetine’s adverse effects. |
| format | Article |
| id | doaj-art-7cd5656d94474d7da61c0fbde0e50ad5 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-7cd5656d94474d7da61c0fbde0e50ad52025-02-04T06:31:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.15364381536438Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessmentDiana Ilyaskina0Yumi Nakadera1Yumi Nakadera2Marja H. Lamoree3Joris M. Koene4Pim E. G. Leonards5Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, NetherlandsSenckenberg Ocean Species Alliance, Senckenberg Research Institute and Natural History Museum Frankfurt, Frankfurt, GermanyAmsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, NetherlandsPharmaceuticals such as selective serotonin reuptake inhibitors (SSRIs), are increasingly detected in aquatic environments, posing potential risks to non-target organisms, because many of those substances are widely shared neuromodulator. In this study, we investigated the effects of SSRI antidepressant, namely, fluoxetine, exposure on the freshwater snail L. stagnalis, focusing on egg development, neurochemical pathways, and lipid metabolism. Snails were exposed to a range of 51–434 µg fluoxetine L⁻1 for 7 days, followed by analysis of survival, feeding behaviour, reproduction, and metabolomic changes in the central nervous system (CNS), albumen gland, and eggs. Although no significant effects were observed on survival or fecundity, fluoxetine exposure significantly impaired egg development in a dose-dependent manner, reducing hatching rates with an EC50 of 126 µg fluoxetine L⁻1. Removal of eggs from the contaminated environment partially reversed these developmental effects, suggesting potential recovery if fluoxetine levels decrease. Molecular analysis revealed several neurochemical and lipidomic alterations. In the CNS, elevated levels of catecholamines, phosphatidylcholines (PC), and ceramides were linked to disruptions in neurotransmission, membrane integrity, and impaired embryo development. In the albumen gland, we detected a decrease of key lipid classes, including sphingomyelins and fatty acids, which can be linked with impaired egg quality. Additionally, a decrease in histamine in both the albumen gland and eggs suggested further disruption of egg development, potentially affecting metamorphosis success. Moreover, the dose-dependent increase in choline, along with PC and oxidized PC, indicated oxidative stress and lipid peroxidation in the CNS and exposed eggs of Lymnaea stagnalis. Our findings highlight the benefits of combining behavioral assessments with metabolomic profiling to better understand the mechanistic pathways underlying fluoxetine’s adverse effects.https://www.frontiersin.org/articles/10.3389/fphar.2025.1536438/fullfluoxetineLymnaea stagnalislipid metabolismecotoxicologyneurochemical pathways |
| spellingShingle | Diana Ilyaskina Yumi Nakadera Yumi Nakadera Marja H. Lamoree Joris M. Koene Pim E. G. Leonards Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment Frontiers in Pharmacology fluoxetine Lymnaea stagnalis lipid metabolism ecotoxicology neurochemical pathways |
| title | Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment |
| title_full | Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment |
| title_fullStr | Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment |
| title_full_unstemmed | Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment |
| title_short | Impact of fluoxetine exposure on Lymnaea stagnalis and its developing eggs: integrating untargeted lipidomics, targeted metabolomics, and classical risk assessment |
| title_sort | impact of fluoxetine exposure on lymnaea stagnalis and its developing eggs integrating untargeted lipidomics targeted metabolomics and classical risk assessment |
| topic | fluoxetine Lymnaea stagnalis lipid metabolism ecotoxicology neurochemical pathways |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1536438/full |
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