Shen Yawei, Brown Cameron E, Li Xiao, Zhang Peng, McGee Stacey R, Spina Søren C, Loret de Mola J Ricardo, Fiddler Joanna L, Wu Haodi, Liu Qing
Department of Biological Sciences, Clemson University, Clemson, SC, USA.
Center for Human Genetics, Clemson University, Greenwood, SC, 29646, USA.
Commun Biol. 2025 May 12;8(1):736. doi: 10.1038/s42003-025-08168-8.
The administration of selective serotonin reuptake inhibitors (SSRIs) during pregnancy can increase the odds of congenital heart defects in babies. The present study aims to explore the toxic effects of SSRIs on the cardiac systems and the underlying mechanism. We apply human pluripotent stem cells to establish 2D-monolayer cardiomyocyte and 3D-cardiac organoid models to evaluate the effects of three SSRIs (fluoxetine, paroxetine, and sertraline) on cardiac development. We observe that SSRIs exposure inhibited ATP production and mitochondrial respiration and disrupted mitochondrial homeostasis and sarcomere structure in the differentiating cardiomyocytes, presenting high risks of dysfunction and abnormality of cardiomyocytes. Further analyses in the cardiac organoid model show that SSRIs not only reduce mitochondrial respiration and ATP production, but may also affect cardiac development and angiogenesis. Altogether, our study reveals that SSRIs induce mitochondrial dysfunction and sarcomeric disorganization in cardiomyocytes, implying their potential risk to the cardiac system.
孕期服用选择性5-羟色胺再摄取抑制剂（SSRI）会增加婴儿患先天性心脏缺陷的几率。本研究旨在探究SSRI对心脏系统的毒性作用及其潜在机制。我们应用人类多能干细胞建立二维单层心肌细胞和三维心脏类器官模型，以评估三种SSRI（氟西汀、帕罗西汀和舍曲林）对心脏发育的影响。我们观察到，暴露于SSRI会抑制分化中的心肌细胞的ATP生成和线粒体呼吸，破坏线粒体稳态和肌节结构，呈现出心肌细胞功能障碍和异常的高风险。在心脏类器官模型中的进一步分析表明，SSRI不仅会降低线粒体呼吸和ATP生成，还可能影响心脏发育和血管生成。总之，我们的研究表明，SSRI会诱导心肌细胞中的线粒体功能障碍和肌节紊乱，这意味着它们对心脏系统存在潜在风险。
