Evidence mapPaperPMID 40719844Full record

ArticlePharmacological reports : PR2025

The sertraline metabolite, desmethylsertraline, may be implicated in adverse outcomes reported after gestational sertraline use: insights from a study in zebrafish.

Cassius M Phogole, Lesha Pretorius, Tracy Kellermann, Maré Vlok, Carine Smith

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Article in Pharmacological reports : PR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Cassius M PhogoleDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID https://orcid.org/0000-0003-2973-0878
Lesha PretoriusExperimental Medicine Group, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID https://orcid.org/0000-0001-9906-9785
Tracy KellermannDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID https://orcid.org/0000-0003-1542-4976
Maré VlokCentral Analytical Facility: Mass Spectrometry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Carine SmithExperimental Medicine Group, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. csmith@sun.ac.za.ORCID https://orcid.org/0000-0001-5924-9204

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSertraline (SER) is a selective serotonin reuptake inhibitor (SSRI) prescribed for depression, including during pregnancy. Existing literature suggests a potential association between gestational SER use and cardiac and neurodevelopmental anomalies in exposed offspring. This study evaluated the relative impacts of SER and its metabolite desmethylsertraline (DES) on the proteome during early development.

methodsZebrafish embryos and larvae were exposed to individual treatments of translated umbilical cord-blood equivalent concentrations of SER or DES during early developmental stages. Quantified activity tracking and protein expression levels of serotonin transporter (SERT) were used to confirm a significant SSRI effect in exposed larvae. A whole-larvae proteomic analysis was conducted using a label-free quantitative liquid chromatography-mass spectrometry approach. Protein identification was performed using zebrafish and human protein databases.

resultsApparent therapeutic SSRI effect of exposure doses of SER and DES was confirmed in zebrafish larvae, by reduced activity levels, as well as decreased SERT. DES, but not SER, resulted in several differentially regulated proteins, identified in both the zebrafish and human databases. The results from the two databases correlated and aligned with an increased risk for cardiovascular and neurodevelopmental dysregulation.

conclusionProteomic data suggest that DES, rather than SER, at physiologically relevant doses, may be responsible for adverse clinical outcomes reported after gestational SSRI use. Current data positions larval zebrafish as a possible tool for assessment of long-term risk after gestational SER use, as well as a drug development tool in this context. CLINICAL TRIAL NUMBER: N/A.

Indexed as

Selective Serotonin Reuptake InhibitorsSertralineAnimalsFemaleHumansLarvaPregnancyProteomicsSerotonin Plasma Membrane Transport ProteinsZebrafishSelective Serotonin Reuptake InhibitorsSerotonin Plasma Membrane Transport ProteinsSertralineCardiovascular riskEquivalent doseLarvaeLocomotionProteomicsSERTSSRI

Identifiers

PMID40719844
PMCPMC12443929

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.