Higher Mitochondrial DNA Content in Human IUGR Placenta

Lattuada, D.; Colleoni, F.; Martinelli, A.; Garretto, A.; Magni, R.; Radaelli, T.; Cetin, I.

doi:10.1016/j.placenta.2008.09.012

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Volume 29, Issue 12 , Pages 1029-1033, December 2008

Higher Mitochondrial DNA Content in Human IUGR Placenta

D. Lattuada
- Institute of Obstetrics and Gynecology I “L. Mangiagalli”, University of Milano, IRCCS Policlinico, Mangiagalli and Regina Elena, via Della Commenda 12, 20122 Milano, Italy
F. Colleoni
- Department of Clinical Sciences, Ospedale Luigi Sacco, University of Milano, Milano, Italy
A. Martinelli
- Department of Clinical Sciences, Ospedale Luigi Sacco, University of Milano, Milano, Italy
A. Garretto
- Department of Clinical Sciences, Ospedale Luigi Sacco, University of Milano, Milano, Italy
R. Magni
- Institute of Obstetrics and Gynecology I “L. Mangiagalli”, University of Milano, IRCCS Policlinico, Mangiagalli and Regina Elena, via Della Commenda 12, 20122 Milano, Italy
T. Radaelli
- Institute of Obstetrics and Gynecology I “L. Mangiagalli”, University of Milano, IRCCS Policlinico, Mangiagalli and Regina Elena, via Della Commenda 12, 20122 Milano, Italy
I. Cetin
- Department of Clinical Sciences, Ospedale Luigi Sacco, University of Milano, Milano, Italy
- Corresponding author. Unit of Obstetrics and Gynecology, Hospital “Luigi Sacco”, via G.B. Grassi, 74, 20157 Milano, Italy. Tel.: +39 0250319804; fax: +39 0250319805.

Accepted 22 September 2008. published online 13 November 2008.

Abstract

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 pO₂, 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.

Keywords: Mitochondrial DNA content, IUGR, Placenta