Effects of Gestational Hypoxia on PGC1α and Mitochondrial Acetylation in Fetal Guinea Pig Hearts.
Effects of Gestational Hypoxia on PGC1α and Mitochondrial Acetylation in Fetal Guinea Pig Hearts.
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DOI：
10.1007/s43032-023-01245-5
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发表时间：
2023-10
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影响因子：
--
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中科院分区：
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--
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慢性宫内缺氧是一种重要的妊娠并发症，影响胎儿心脏的生长、代谢和线粒体功能，有助于后代的心血管编程。前列环素α(Peroxisome Proplator-Actiated Reptorγco-Actifator 1α)是线粒体生物发生的主要调控因子。我们研究了不同胎龄暴露后低氧对前列腺素C_1α表达的影响。时间交配的妊娠豚鼠在25天(早孕)和50天(晚孕)分别暴露于常氧(NMX，21%O2)或低氧(HPX，10.5%O2)，并在足月(足月=~65天)时取出胎儿。检测胎鼠心肌细胞核PGC1SIRT1、AMPK和线粒体SIRT3的α表达、SIRT3活性和线粒体乙酰化程度。早期低氧增加胎儿心肌细胞核Pgc1α，对生长受限男性和女性的线粒体乙酰化均无影响。迟发性低氧对雄性和雌性大鼠PCC1mRNA的表达无影响或降低(P<；0.05)，但增加了线粒体乙酰化(P<；0.05)。低氧对SIRT1、AMPK、SIRT3表达和SIRT3活性的影响因性别而异。胎儿心脏对缺氧的反应能力因孕周、暴露年龄和胎儿性别而异。此外，迟发性缺氧对胎儿心脏功能的影响给男性胎儿带来的风险比女性胎儿更大，这与后代的心血管编程效应有关。
Chronic intrauterine hypoxia is a significant pregnancy complication impacting fetal heart growth, metabolism, and mitochondrial function, contributing to cardiovascular programming of the offspring. PGC1α (peroxisome proliferator-activated receptor γ co-activator 1α) is the master regulator of mitochondrial biogenesis. We investigated the effects of hypoxia on PGC1α expression following exposure at different gestational ages. Time-mated pregnant guinea pigs were exposed to normoxia (NMX, 21% O2) or hypoxia (HPX, 10.5% O2) at either 25-day (early-onset) or 50-day (late-onset) gestation, and all fetuses were extracted at term (term = ~65-day gestation). Expression of nuclear PGC1α, sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and mitochondrial sirtuin 3 (SIRT3) was measured, along with SIRT3 activity and mitochondrial acetylation of heart ventricles of male and female fetuses. Early-onset hypoxia increased (P<0.05) fetal cardiac nuclear PGC1α and had no effect on mitochondrial acetylation of either growth-restricted males or females. Late-onset hypoxia had either no effect or decreased (P<0.05) PCC1α expression in males and females, respectively, but increased (P<0.05) mitochondrial acetylation in both sexes. Hypoxia had variable effects on expression of SIRT1, AMPK, SIRT3, and SIRT3 activity depending on the sex. The capacity of the fetal heart to respond to hypoxia differs depending on the gestational age of exposure and sex of the fetus. Further, the effects of late-onset hypoxia on fetal heart function impose a greater risk to male than female fetuses, which has implications toward cardiovascular programming effects of the offspring.
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影响因子：
3.7
作者：
Foster DB;Liu T;Rucker J;O'Meally RN;Devine LR;Cole RN;O'Rourke B
通讯作者：
O'Rourke B
DOI：
10.3390/antiox10030405
发表时间：
2021-03-08
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
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DOI：
10.1152/ajpregu.00180.2017
发表时间：
2018-07-01
影响因子：
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作者：
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通讯作者：
Morrison, J. L.
DOI：
10.1152/ajpregu.00320.2009
发表时间：
2010-03-01
影响因子：
2.8
作者：
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