Mitochondrial DNA in Placenta: Associations with Fetal Growth and Superoxide Dismutase Activity

Abstract

Background: Prenatal growth restraint is associated with increased oxidative stress - as judged by mitochondrial dysfunction - in pregnancies complicated by preeclampsia or diabetes, but it is uncertain whether this is also the case in uncomplicated pregnancies. We assessed the link between fetal growth restraint and placental mitochondrial dysfunction, as reflected by changes in mitochondrial DNA (mtDNA) content and superoxide dismutase (SOD) activity. Methods: After uncomplicated pregnancies, placentas (n = 48) were collected at term delivery of singleton infants who were appropriate for gestational age (AGA) or small for gestational age (SGA) (n = 24 in each subgroup). Placental mtDNA content was assessed by real-time PCR, placental SOD activity by colorimetry, and citrate synthase activity - to determine mitochondrial mass - by the spectrophotometric method. Results: Placentas of SGA infants had a lower mtDNA content (p = 0.015) and a higher SOD activity (p = 0.001) than those of AGA controls. These differences were maintained after normalization of the mtDNA content by citrate synthase activity. In placentas of SGA infants, there was a negative association between mtDNA content and SOD activity (r = -0.58, p = 0.008). Conclusions: Fetal growth restraint is accompanied by adaptive changes in the mitochondrial function of the placenta, also in uncomplicated pregnancies.

Proteomics Analysis Reveals Abnormal Electron Transport and Excessive Oxidative Stress Cause Mitochondrial Dysfunction in Placental Tissues of Early‐Onset Preeclampsia

“…Mitochondria, as an organelle consumed mostly oxygen, regulated the intracellular oxygen concentration, and produced abundant endogenous ROS, which performed the oxidative phosphorylation process and supplied adequate energy to maintain the integrated function of the placenta. Numerous studies indicated that mitochondrial metabolism of the placenta in pregnancy stage was significantly increased, generating abundant ROS and further induced oxidative stress . An increasing in abundance of ROS would injure vascular endothelial cells and induce uterine spiral artery constriction, and these processes were linked to the occurrence of pregnancy complications, including PE and IUGR …”

Ozone-induced fetal growth restriction in rats is associated with sexually dimorphic placental and fetal metabolic adaptation

“…We focused on alterations in placental mitochondrial bioenergetics due to the important roles that mitochondria play in nutrient and oxygen utilization. IUGR has been associated with both increases [ 22 , 24 , 40 ] and decreases [ 45 , 46 ] in placental mitochondrial content. In our growth-restriction model, mitochondrial density markers were elevated in the placental tissue from both sexes.…”

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

“…In another study, however, in a baboon model of maternal protein restriction, the expression of mitochondrialrelated genes was affected to a greater extent in female than male fetuses with subsequently reduced mRNA expression of mitochondrial respiratory chain transcripts in both sexes (301). Furthermore, mitochondrial DNA content was reduced in SGA infants, and SOD activity was increased (98) in a possible compensatory manner. In placental trophoblast cultures, increased maternal adiposity was associated with reduced mitochondrial respiratory function despite a 6-to 14-fold higher production of ROS (254).…”