Journal article
Hypersensitivity of Zebrafish htr2b Mutant Embryos to Sertraline Indicates a Role for Serotonin Signaling in Cardiac Development
Journal of cardiovascular pharmacology, Vol.80(2), pp.261-269
05/19/2022
DOI: 10.1097/FJC.0000000000001297
PMCID: PMC9354722
PMID: 35904815
Abstract
Supplemental Digital Content is Available in the Text.
Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the United States. Maternal use of SSRIs has been linked to an elevated rate of congenital heart defects, but the exact mechanism of pathogenesis is unknown. Previously, we have shown a decrease in cardiomyocyte proliferation, left ventricle size, and reduced cardiac expression of the serotonin receptor 5-HT
2B
in offspring of mice exposed to the SSRI sertraline during pregnancy, relative to offspring of untreated mice. These results suggest that disruption of serotonin signaling leads to heart defects. Supporting this conclusion, we show here that zebrafish embryos exposed to sertraline develop with a smaller ventricle, reduced cardiomyocyte number, and lower cardiac expression of
htr2b
relative to untreated embryos. Moreover, zebrafish embryos homozygous for a nonsense mutation of
htr2b
(
htr2b
sa16649
) were sensitized to sertraline treatment relative to wild-type embryos. Specifically, the ventricle area was reduced in the homozygous
htr2b
mutants treated with sertraline compared with wild-type embryos treated with sertraline and homozygous
htr2b
mutants treated with vehicle control. Whereas long-term effects on left ventricle shortening fraction and stroke volume were observed by echocardiography in adult mice exposed to sertraline in utero, echocardiograms of adult zebrafish exposed to sertraline as embryos were normal. These results implicate the 5-HT
2B
receptor functions in heart development and suggest zebrafish are a relevant animal model that can be used to investigate the connection between maternal SSRI use and elevated risk of congenital heart defects.
Details
- Title: Subtitle
- Hypersensitivity of Zebrafish htr2b Mutant Embryos to Sertraline Indicates a Role for Serotonin Signaling in Cardiac Development
- Creators
- Mitchell E. Kent - Department of Pediatrics.Bo Hu - Department of Anatomy and Cell Biology.Timothy M. Eggleston - Department of Pediatrics.Ryan S. Squires - Department of Pediatrics.Kathy A. Zimmerman - University of IowaRobert M. Weiss - University of IowaRobert D. Roghair - Department of Pediatrics.Fang Lin - Department of Anatomy and Cell Biology.Robert A. Cornell - Department of Anatomy and Cell Biology.Sarah E. Haskell - Department of Pediatrics.
- Resource Type
- Journal article
- Publication Details
- Journal of cardiovascular pharmacology, Vol.80(2), pp.261-269
- DOI
- 10.1097/FJC.0000000000001297
- PMID
- 35904815
- PMCID
- PMC9354722
- NLM abbreviation
- J Cardiovasc Pharmacol
- ISSN
- 0160-2446
- eISSN
- 1533-4023
- Publisher
- Journal of Cardiovascular Pharmacology
- Language
- English
- Date published
- 05/19/2022
- Academic Unit
- Critical Care; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Neonatology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984353824902771
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