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Placental mitochondrial DNA mutations and copy numbers in intrauterine growth restricted (IUGR) pregnancy
Mitochondrion ( IF 4.4 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.mito.2020.08.008
Ritam Naha 1 , Akheel Anees 1 , Sanjiban Chakrabarty 1 , Punitkumar Shankar Naik 1 , Megha Pandove 2 , Deeksha Pandey 2 , Kapaettu Satyamoorthy 1
Affiliation  

Intrauterine Growth Restriction (IUGR) is a common and significant complication that arises during pregnancy wherein the fetus fails to attain its full growth potential. Mitochondria being one of the primary sources of energy, plays an important role in placentation and fetal development. In IUGR pregnancy, increased oxidative stress due to inadequate oxygen and nutrient supply could possibly alter mitochondrial functions and homeostasis. In this study, we evaluated the biochemical and molecular changes in mitochondria as biosignature for early and better characterization of IUGR pregnancies. We identified significant increase in mtDNA copy number in both IUGR (p= 0.0001) and Small for Gestational Age (SGA) but healthy (p=0.0005) placental samples when compared to control. Whole mitochondrial genome sequencing identified novel mutations in both coding and non-coding regions of mtDNA in multiple IUGR placental samples. Sirtuin-3 (Sirt3) protein expression was significantly downregulated (p=0.027) in IUGR placenta but there was no significant difference in Nrf1 expression in IUGR when compared to control group. Our study provides an evidence for altered mitochondrial homeostasis and paves a way towards interrogating mitochondrial abnormalities in IUGR pregnancies.

中文翻译:

宫内生长受限 (IUGR) 妊娠中胎盘线粒体 DNA 突变和拷贝数

宫内生长受限 (IUGR) 是一种常见且重要的并发症,发生在怀孕期间,胎儿无法充分发挥其生长潜力。线粒体是能量的主要来源之一,在胎盘和胎儿发育中起着重要作用。在 IUGR 妊娠中,由于氧气和营养供应不足导致氧化应激增加可能会改变线粒体功能和体内平衡。在这项研究中,我们评估了线粒体的生化和分子变化,作为早期和更好地表征 IUGR 妊娠的生物特征。与对照相比,我们发现 IUGR (p=0.0001) 和小于胎龄 (SGA) 但健康 (p=0.0005) 胎盘样本的 mtDNA 拷贝数显着增加。全线粒体基因组测序在多个 IUGR 胎盘样本中发现了 mtDNA 编码区和非编码区的新突变。Sirtuin-3 (Sirt3) 蛋白表达在 IUGR 胎盘中显着下调 (p=0.027),但与对照组相比,IUGR 中 Nrf1 的表达没有显着差异。我们的研究为线粒体稳态改变提供了证据,并为研究 IUGR 妊娠中的线粒体异常铺平了道路。
更新日期:2020-11-01
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