Fetal Programming and Sexual Dimorphism of Mitochondrial Protein Expression and Activity of Hearts of Prenatally Hypoxic Guinea Pig Offspring.
Fetal Programming and Sexual Dimorphism of Mitochondrial Protein Expression and Activity of Hearts of Prenatally Hypoxic Guinea Pig Offspring.
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胎儿编程和产前缺氧豚鼠后代线粒体蛋白表达和心脏活性的性别二态性。
DOI：
10.1155/2019/7210249
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发表时间：
2019
影响因子：
--
通讯作者：
Polster,BrianM
中科院分区：
文献类型：
--
作者：
Thompson,LorenP;Song,Hong;Polster,BrianM
慢性宫内缺氧是心血管功能障碍的编程刺激因素。虽然胎儿心脏适应了氧合减少，但后代心脏在成年后却容易受到随后的代谢挑战。心脏线粒体是负责有效能量供应的关键细胞器，但在缺氧条件下容易受到损害。我们认为宫内缺氧会改变线粒体功能，作为后代收缩功能障碍的潜在编程机制。在足月前（65天）暴露于产前缺氧（10.5％O2）14天的90天龄雄性和雌性后代的心脏中测量线粒体功能指数，例如线粒体DNA含量、复合物（C）I-V表达和CI/CIV酶活性。男性心脏中左心室组织和心肌细胞线粒体 DNA 含量、CIV 表达和 CI/CIV 活性均降低。在女性心肌细胞中，缺氧对 CI-CV 蛋白表达和 CI/CIV 活性没有影响。这项研究表明，慢性宫内缺氧改变了特定呼吸复合体的内在特性，作为后代心脏功能障碍的编程机制。线粒体功能的性别差异可能是年龄匹配的男性比女性更容易患心血管疾病和心力衰竭的原因。
Chronic intrauterine hypoxia is a programming stimulus of cardiovascular dysfunction. While the fetal heart adapts to the reduced oxygenation, the offspring heart becomes vulnerable to subsequent metabolic challenges as an adult. Cardiac mitochondria are key organelles responsible for an efficient energy supply but are subject to damage under hypoxic conditions. We propose that intrauterine hypoxia alters mitochondrial function as an underlying programming mechanism of contractile dysfunction in the offspring. Indices of mitochondrial function such as mitochondrial DNA content, Complex (C) I‐V expression, and CI/CIV enzyme activity were measured in hearts of male and female offspring at 90 days old exposed to prenatal hypoxia (10.5% O2) for 14 d prior to term (65 d). Both left ventricular tissue and cardiomyocytes exhibited decreased mitochondrial DNA content, expression of CIV, and CI/CIV activity in male hearts. In female cardiomyocytes, hypoxia had no effect on protein expression of CI‐CV nor on CI/CIV activity. This study suggests that chronic intrauterine hypoxia alters the intrinsic properties of select respiratory complexes as a programming mechanism of cardiac dysfunction in the offspring. Sex differences in mitochondrial function may underlie the increased vulnerability of age‐matched males compared to females in cardiovascular disease and heart failure.