Lattuada D, Colleoni F, Martinelli A, Garretto A, Magni R, Radaelli T, Cetin I
Institute of Obstetrics and Gynecology I "L. Mangiagalli", University of Milano, IRCCS Policlinico, Mangiagalli and Regina Elena, via Della Commenda 12, 20122 Milano, Italy.
Placenta. 2008 Dec;29(12):1029-33. doi: 10.1016/j.placenta.2008.09.012. Epub 2008 Nov 12.
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.
宫内生长受限（IUGR）与特定的胎盘表型相关，该表型会降低特定营养物质的摄取。最近，有人提出IUGR可能在妊娠早期就已确定。这一时期的特点是蜕膜滋养层侵入以及强烈的细胞生长、复制和分化。由于妊娠期间需要大量的能量供应，我们推测线粒体作为细胞中的主要能量生产者，可能在这一过程中发挥关键作用。本研究的目的是调查线粒体在IUGR发病机制中的作用，通过评估IUGR胎盘与对照胎盘中线粒体DNA拷贝数（mtDNA）来进行研究。在择期剖宫产时，从50例单胎妊娠中采集胎盘样本。26例妊娠为宫内生长正常（AGA）的对照，24例在宫内诊断为IUGR后进行研究。所有样本均通过实时定量PCR进行分析，并通过非参数检验进行统计分析。AGA胎盘和IUGR胎盘中线粒体DNA含量的中位数（IQR）有显著差异（分别为455和698，p = 0.004）。导致观察到差异的细胞类型尚不清楚，细胞类型比例的变化可能会影响这一测量结果。此外，观察到mtDNA与脐静脉pO₂之间存在显著的负相关关系，根据多普勒检查结果和子痫前期的存在情况，在最严重的IUGR病例中检测到的水平最高。这些数据表明IUGR发病机制与胎盘mtDNA拷贝数增加之间存在关联。从我们的结果可以推测，mtDNA增加代表胎盘代谢机制对胎儿热量限制的一种适应。此外，我们发现这种增加与脐静脉中的氧张力呈负相关。虽然不能暗示其有特定的致病作用，但在IUGR胎盘中，mtDNA会随着缺氧而增加。
