Department of Cellular and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India.
Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India.
Mitochondrion. 2020 Nov;55:85-94. doi: 10.1016/j.mito.2020.08.008. Epub 2020 Aug 28.
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.
胎儿宫内生长受限（IUGR）是一种常见且严重的妊娠并发症，胎儿未能充分发挥其生长潜能。线粒体作为主要的能量来源之一，在胎盘形成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的氧化应激增加，可能会改变线粒体的功能和动态平衡。在这项研究中，我们评估了线粒体的生化和分子变化，作为早期更好地描述 IUGR 妊娠的生物标志物。与对照组相比，我们发现 IUGR（p=0.0001）和小胎龄儿（SGA）但健康（p=0.0005）胎盘样本中的 mtDNA 拷贝数显著增加。全线粒体基因组测序在多个 IUGR 胎盘样本的编码和非编码区域中发现了新的突变。Sirtuin-3（Sirt3）蛋白表达在 IUGR 胎盘中显著下调（p=0.027），但与对照组相比，IUGR 中 Nrf1 的表达没有显著差异。我们的研究提供了线粒体动态平衡改变的证据，并为研究 IUGR 妊娠中的线粒体异常铺平了道路。
