Am J Obstet Gynecol. 2010 Oct;203(4):365.e1-6. doi: 10.1016/j.ajog.2010.05.027. Epub 2010 Jul 8.
Higher mitochondrial DNA content in human IUGR placenta.
Lattuada D (Institute of Obstetrics and Gynecology I “L. Mangiagalli”, University of Milano, IRCCS Policlinico, Mangiagalli and Regina Elena, via Della Commenda 12, 20122 Milano, Italy.), Colleoni F, Martinelli A, Garretto A, Magni R, Radaelli T, Cetin I.
IUGR has been associated to a specific placental phenotype with reduced uptake of specific nutrients. Recently, it has been hypothesized that IUGR may be determined during early gestation. This period is characterized by decidual trophoblast invasion and by intense cellular growth, replication and differentiation. Since a huge energetic availability is required during gestation, we hypothesize that mitochondria may play a crucial role in this process being the main energetic producer in the cell. The aim of this study was to investigate the role of mitochondria in IUGR pathogenesis, evaluating the number of mitochondrial DNA copies (mtDNA) in IUGR placentae compared to controls. Placental samples were collected from 50 singleton pregnancies at the time of elective caesarean section. Twenty-six pregnancies were controls with normal intrauterine growth (AGA) and 24 were studied after the in utero diagnosis of IUGR. All samples were analyzed by real-time quantitative PCR and statistical analysis was performed by non-parametric tests. The median value of mitochondrial DNA content (IQR) in AGA and IUGR placentae was significantly different (455 and 698, respectively, p=0.004).
The cell types responsible for the difference observed is unknown and it is possible that changes observed in the proportion of cell types may influence this measurement. Moreover, a significant negative relationship was observed between mtDNA and umbilical venous pO(2), with the highest levels detected in the most severe IUGR cases according to Doppler findings and to the presence of preeclampsia. These data suggest a relationship between the pathogenesis of IUGR and increased placental mtDNA copies. From our results we can speculate that increased mtDNA represents an adaptation of the metabolic placental mechanism to the calorie restriction of the fetus. Furthermore, we found that this rise was inversely related to oxygen tension in the umbilical vein. Although no specific pathogenetic role can be implied, mtDNA increases with hypoxia in placentas of IUGR.
Maternal blood mitochondrial DNA content during normal and intrauterine growth restricted (IUGR) pregnancy.
Colleoni F (Unit of Obstetrics and Gynecology, Department of Clinical Sciences L.Sacco and Center for Fetal Research Giorgio Pardi, University of Milan, Milan, Italy.), Lattuada D, Garretto A, Massari M, Mandò C, Somigliana E, Cetin I.
We investigated mitochondrial DNA (mtDNA) content in the maternal circulation of normal pregnancies of different gestational ages and in pregnancies complicated by intrauterine growth restriction (IUGR).
We examined 70 maternal blood samples: 13 nonpregnant women; 45 normal pregnancies, divided into the 3 trimesters; and 12 pregnancies complicated by IUGR. MtDNA content was determined by real-time quantitative polymerase chain reaction, using a genomic control and a target gene.
A highly significant progressive reduction in circulating mtDNA was observed in pregnant women of first, second, and third trimesters and compared to nonpregnant women (mean value: 237, 188, 144, and 283, respectively; P < .001). Moreover, mtDNA was significantly increased in women carrying IUGR fetuses compared to women with normal pregnancies (430 vs 144; P < .001).
MtDNA could provide new insight into the mechanisms that occur during physiological gestation. Furthermore, mtDNA content may help recognize the IUGR disease in pregnancy.
Different mtDNA content of maternal blood in normal pregnancies of different gestational ages and in pregnancies complicated by IUGR.
F. Colleoni , D. Lattuada , A. Garretto , A. Martinelli , C. Mandò , R. Magni, I. Cetin ( presentato all’SGI 2009 di Glasgow )