Abstract
Abstract P3108: Mouse In Utero Plus Neonatal Sertraline Exposure May Result In A Sex-dependent Risk Of Myocardial Infarction In Adulthood
Circulation research, Vol.133(Suppl_1)
08/04/2023
DOI: 10.1161/res.133.suppl_1.P3108
Abstract
Abstract only Background: We previously reported that sertraline reduced left ventricular size, acutely slowed down mouse pup growth, and significantly reduced calcium oscillations in cardiomyocytes (p<0.05), and that the sertraline-induced up-regulations of certain miRNAs might epigenetically modulate cardiac functional gene expression of serotonin signaling pathway with down-regulation of Htr2a, Htr2b and Slc6a4 mRNAs and corresponding proteins (p<0.05). Here we hypothesize that sertraline effect is gender related when subjected to a stress at adult. Method: C57BL/6 adult female mice received sertraline (5 mg/kg/d IP) or saline 5 days before mating, throughout pregnancy until time of delivery, and the pups were given 1/3 adult dose before weaning. At age of 10 weeks, offspring mice were subjected to echocardiograms before myocardial infarction (MI) induced by left anterior descending coronary artery ligation. Mice were divided into groups according to sex, and treatments (saline vs sertraline, & MI vs sham). Ten weeks post-MI, echocardiograms were performed again for the survived mice. Results: Female mice before MI had significantly reduced heart rates (649±18 vs 691±7 bmp), increased end systolic volumes (4.5±0.6 vs 3.2±0.1 μL), and decreased ejection fractions (EF) (80.6±0.7% vs 83.9±0.6%) (n=34, p<0.05). Male mice did not show the significant effects on baseline. Two weeks post-MI, Females had survival rates reduced by sertraline (74.3% vs saline 100%, p=0.0833). Males exhibited MI intolerance with lower survival rates (66.8% vs saline 67.2%), and ODD ratio was deteriorated (24.35 vs female 1.00, p=0.0317). At the end point, the survived mice showed variable MI-induced ischemia zones (47.5±13.2%) corresponding to variable EF (30.0±14.9%). The cardiac functions became not significant different in both male and female survived mice. Concluding Remarks: The cardiac potential risk was observed in the baseline and in the earlier MI phase of female mice with in utero plus neonatal sertraline exposure, while male mice showed different pattern of sertraline effect. Such sex-dependent cardiac effects of maternal SSRI exposure in adult offspring deserve to be detailly studied by using mouse models for heavy use of SSRIs in pregnant women.
Details
- Title: Subtitle
- Abstract P3108: Mouse In Utero Plus Neonatal Sertraline Exposure May Result In A Sex-dependent Risk Of Myocardial Infarction In Adulthood
- Creators
- Yongjun Lu - University of IowaElizabeth Kenkel - Seattle UniversityKathy Zimmerman - University of IowaRobert M Weiss - University of IowaRobert Roghair - University of IowaSarah E Haskell - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.133(Suppl_1)
- DOI
- 10.1161/res.133.suppl_1.P3108
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/04/2023
- Academic Unit
- Stead Family Department of Pediatrics; Internal Medicine; Cardiovascular Medicine; Critical Care; Neonatology
- Record Identifier
- 9984479659502771
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