Placental mitochondrial DNA mutations and copy numbers in intrauterine growth restricted (IUGR) pregnancy

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.