Sertraline exposure during development may impact post‐myocardial infarction survival in adult mice

TL;DR

Exposure to sertraline during development in mice leads to sex-specific changes in heart function and survival after heart attacks.

Contribution

The study reveals sex-specific cardiac effects of developmental sertraline exposure and its impact on post-MI outcomes in mice.

Findings

Sertraline-exposed female mice had reduced heart rate and ejection fraction before MI.

Sertraline-exposed male mice showed higher scar-zone collagen and a trend of lower survival after MI.

Serotonin-related gene expression was altered in sertraline-exposed mice, especially in males.

Abstract

This study examines sex‐specific effects of developmental sertraline exposure on cardiac function and gene expression before and after myocardial infarction (MI) in mice. Female C57BL/6 mice (10 weeks) received intraperitoneal sertraline (5 mg/kg/day, n = 37) or saline (n = 20) before mating, during pregnancy, and postnatally to pups (1.5 mg/kg/day, postnatal Days 0–14). MI in offspring was induced at 10 weeks by left coronary artery ligation. Randomly chosen offspring (sham n = 8 and MI n = 26 per sex) underwent baseline echocardiography and at 10 weeks post‐MI if surviving. Serotonin‐ and estrogen‐related gene expression was analyzed. Before MI, sertraline‐exposed females had lower heart rate (649.1 ± 102.0 vs. 692.9 ± 38.4 bpm, n = 34), increased end‐systolic volume, and reduced ejection fraction (80.7 ± 6.3% vs. 83.9 ± 3.5%; p < 0.05). Exposed males also had lower heart rates (665.9 ± 32.7 vs. 683.3 ± 47.9 bpm, n = 34, p < 0.05). Post‐MI, both sexes remodeled similarly (scar size, ischemic‐zone fraction); sertraline‐exposed males had higher scar‐zone collagen (p < 0.05) and a nonsignificant lower survival trend than females. Sertraline altered serotonin‐related gene expression (Htr2a, Htr2b, Slc6a4), particularly in male sham mice. Developmental sertraline exposure induces sex‐specific cardiac changes, potentially affecting post‐MI outcomes, with males showing more structural and survival impairments.

The impact of developmental sertraline exposure on post‐myocardial infarction (MI) outcomes.

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