Abstract：
BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to congenital heart disease and fetal alcohol syndrome. The heart primarily relies on mitochondria to generate energy, so impaired mitochondrial function due to alcohol exposure can significantly affect cardiac development and function. Our study aimed to investigate the impact of PAE on myocardial and mitochondrial functions in offspring mice.
METHODS: We administered 30% alcohol (3 g/kg) to pregnant C57BL/6 mice during the second trimester. We assessed cardiac function by transthoracic echocardiography, observed myocardial structure and fibrosis through staining tests and electron transmission microscopy, and detected cardiomyocyte apoptosis with dUTP nick end labeling assay and real-time quantitative PCR. Additionally, we measured the reactive oxygen species content, ATP level, and mitochondrial DNA copy number in myocardial mitochondria. Mitochondrial damage was evaluated by assessing the level of mitochondrial membrane potential and the opening degree of mitochondrial permeability transition pores.
RESULTS: Our findings revealed that PAE caused cardiac systolic dysfunction, ventricular enlargement, thinned ventricular wall, cardiac fibrosis in the myocardium, scattered loss of cardiomyocytes, and disordered arrangement of myocardial myotomes in the offspring. Furthermore, we observed a significant increase in mitochondrial reactive oxygen species content, a decrease in mitochondrial membrane potential, ATP level, and mitochondrial DNA copy number, and sustained opening of mitochondrial permeability transition pores in the heart tissues of the offspring.
CONCLUSIONS: These results indicated that PAE had adverse effects on the cardiac structure and function of the newborn mice and could trigger oxidative stress in their myocardia and contribute to mitochondrial dysfunction.
METHODS: We administered 30% alcohol (3 g/kg) to pregnant C57BL/6 mice during the second trimester. We assessed cardiac function by transthoracic echocardiography, observed myocardial structure and fibrosis through staining tests and electron transmission microscopy, and detected cardiomyocyte apoptosis with dUTP nick end labeling assay and real-time quantitative PCR. Additionally, we measured the reactive oxygen species content, ATP level, and mitochondrial DNA copy number in myocardial mitochondria. Mitochondrial damage was evaluated by assessing the level of mitochondrial membrane potential and the opening degree of mitochondrial permeability transition pores.
RESULTS: Our findings revealed that PAE caused cardiac systolic dysfunction, ventricular enlargement, thinned ventricular wall, cardiac fibrosis in the myocardium, scattered loss of cardiomyocytes, and disordered arrangement of myocardial myotomes in the offspring. Furthermore, we observed a significant increase in mitochondrial reactive oxygen species content, a decrease in mitochondrial membrane potential, ATP level, and mitochondrial DNA copy number, and sustained opening of mitochondrial permeability transition pores in the heart tissues of the offspring.
CONCLUSIONS: These results indicated that PAE had adverse effects on the cardiac structure and function of the newborn mice and could trigger oxidative stress in their myocardia and contribute to mitochondrial dysfunction.
摘要：
背景：产前酒精暴露（PAE）与先天性心脏病和胎儿酒精综合征有关。心脏主要依靠线粒体来产生能量,因此，酒精暴露导致的线粒体功能受损会显著影响心脏发育和功能。本研究旨在探讨PAE对子代小鼠心肌和线粒体功能的影响。
方法：我们在妊娠中期对C57BL/6小鼠给予30%酒精（3g/kg）。我们通过经胸超声心动图评估心功能，通过染色试验和透射电镜观察心肌结构和纤维化，用dUTP缺口末端标记法和实时定量PCR法检测心肌细胞凋亡。此外,我们测量了活性氧的含量，ATP水平,和心肌线粒体中的线粒体DNA拷贝数。通过评估线粒体膜电位水平和线粒体通透性转换孔的开放程度来评估线粒体损伤。
结果：我们的发现显示PAE导致心脏收缩功能障碍，心室扩大,心室壁变薄，心肌纤维化，心肌细胞的分散损失，和后代心肌组织的无序排列。此外，我们观察到线粒体活性氧含量显著增加，线粒体膜电位下降,ATP水平,和线粒体DNA拷贝数,子代心脏组织线粒体通透性过渡孔的持续开放。
结论：这些结果表明，PAE对新生小鼠的心脏结构和功能有不利影响，并可引发心肌中的氧化应激并导致线粒体功能障碍。
方法：我们在妊娠中期对C57BL/6小鼠给予30%酒精（3g/kg）。我们通过经胸超声心动图评估心功能，通过染色试验和透射电镜观察心肌结构和纤维化，用dUTP缺口末端标记法和实时定量PCR法检测心肌细胞凋亡。此外,我们测量了活性氧的含量，ATP水平,和心肌线粒体中的线粒体DNA拷贝数。通过评估线粒体膜电位水平和线粒体通透性转换孔的开放程度来评估线粒体损伤。
结果：我们的发现显示PAE导致心脏收缩功能障碍，心室扩大,心室壁变薄，心肌纤维化，心肌细胞的分散损失，和后代心肌组织的无序排列。此外，我们观察到线粒体活性氧含量显著增加，线粒体膜电位下降,ATP水平,和线粒体DNA拷贝数,子代心脏组织线粒体通透性过渡孔的持续开放。
结论：这些结果表明，PAE对新生小鼠的心脏结构和功能有不利影响，并可引发心肌中的氧化应激并导致线粒体功能障碍。
