Placental Mitochondrial DNA and Respiratory Chain Enzymes in the Etiology of Preeclampsia

Abstract

Objective: To evaluate the occurrence of the most common mutations and deletions in mitochondrial DNA and deficiencies in the enzyme complexes of the mitochondrial respiratory chain in placentas from preeclamptic women.Methods: Mitochondria were isolated from the placentas of 17 preeclamptic or 25 control women, and the activities of mitochondrial respiratory chain complexes were measured. Deletions and three common point mutations of mitochondrial DNA were searched for by the Southern blot and polymerase chain reaction (PCR) methods from the same placentas. Results: Mean (؎ standard deviation) mitochondrial respiratory chain enzyme complex activities in placentas onprotein basis (nmol/min/mg of protein) were similar in preeclamptics and controls (nicotinamide adenine dinucleotide, reduced form-ubiquinone oxidoreductase 25.84 ؎ ؎ ؎ 9.29 versus 31.02 ؎ ؎ ؎ 7.52; nicotinamide adenine dinucleotide, reduced form-cytochrome-c oxidoreductase 77.88 ؎ ؎ ؎ 42.24 versus 104.06 ؎ ؎ ؎ 56.73; succinate-cytochrome-c oxidoreductase 57.90 ؎ ؎ ؎ 13.83 versus 64.44 ؎ ؎ ؎ 20.16; cytochrome-c oxidase 106.43 ؎ ؎ ؎ 35.46 versus 128.37 ؎ ؎ ؎ 48.64, respectively) and they were similar also when referenced to the mitochondrial marker enzyme citrate synthase. The sample sizes in both patient and control groups were found to be large enough by post hoc test. Large-scale deletions or the common 5-kb and 7.4-kb deletions were not detected, even at the sensitivity level of PCR. The three most common point mutations were not found in either control or preeclamptic placental samples. Conclusion: Common mitochondrial DNA mutations seem to play no major role in the universal etiology of preeclampsia, as assessed by analysis of the mitochondrial genome and respiratory chain enzyme activities in vitro. This does not exclude possible alterations in the energy state of the preeclamptic placenta. (Obstet Gynecol 1998;91:950 -5. © 1998 by The American College of Obstetricians and Gynecologists.)From the

Preeclampsia and HELLP Syndrome: Impaired Mitochondrial Function in Umbilical Endothelial Cells

“…In accordance with these observations, Vuorinen found that RC enzymes and CS activities tended to be lower in isolated mitochondria of villous portions from PE women. 32 Our findings are in line with the results showing morphological changes by electron microscopy in umbilical endothelial cells from pregnancies complicated by PE. Endothelial cells from diseased pregnancies appeared ultrastructurally separated.…”

“…In contrast, 2 different groups found that common mitochondrial DNA mutations seemed to play no major role in the universal etiology of PE as assessed by analysis of the mitochondrial genome. 22,32 However, the inhibition of one of the enzymes or metabolic pathways may lead to secondary impairment of further biochemical processes in mitochondria. Reduced capacities of FAO for example lead to the accumulation of acyl-CoA-esters and acylcarnitines, as shown in our study for mothers and their infants from complicated pregnancies.…”

Placental mitochondria and reactive oxygen species in the physiology and pathophysiology of pregnancy

“…Placental ER stress occurs in pregnancies affected by GDM and preeclampsia . Preeclamptic placentae have decreases in intracellular Ca 2+ and decreased expression of ETS enzymes, which are associated with ER dysfunction. Further, ER stress markers GRP78, phospho‐PERK, X‐box binding protein1 (XBP1) and eukaryotic initiation factor 2 alpha (eiF2α) increase in response to inducible nitric oxide synthase (iNOS) in preeclampsia .…”

Mitochondrial DNA Copy Number in Peripheral Blood in the First Trimester of Pregnancy and Different Preeclampsia Clinical Phenotypes Development: A Pilot Study

“…Mutations in the mitochondrial genes coding for respiratory chain enzymes and anomalies in mitochondrial DNA content, activity, and ultrastructure have been extensively described in placentas of women affected by PE. [35][36][37][38][39][40][41] Even if less exhaustively, also the potential association between peripheral blood mtDNA content and PE has been investigated. Qiu et al measured free mtDNA content in blood samples (ie, noncellular mitochondrial DNA) collected during labor and delivery.…”