Mandò 2014 Am J Physiol Endocrinol Metab
|Mandò C, De Palma C, Stampalija T, Anelli GM, Figus M, Novielli C, Parisi F, Clementi E, Ferrazzi E, Cetin I (2014) Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia. Am J Physiol Endocrinol Metab 306:E404-13.|
Abstract: Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such as preeclampsia (PE) associated with IUGR share a common placental phenotype called "placental insufficiency" originating in early gestation, when high availability of energy is required. Here, we assess mitochondrial content and the expression and activity of respiratory chain complexes (RCC) in placental cells of these pathologies. We measured mitochondrial DNA (mtDNA) and Nuclear Respiratory Factor 1 (NRF1) expression in placental tissue and cytotrophoblast cells, gene and protein expressions of RCC (Real Time PCR and Western Blotting) and their oxygen consumption, using the innovative technique of High Resolution Respirometry. We analyzed eight IUGR, six PE and eight uncomplicated human pregnancies delivering by elective cesarean section. We found lower mRNA levels of complex II, III and IV in IUGR cytotrophoblast cells, but no differences at the protein level, suggesting a post-transcriptional compensatory regulation. mtDNA was increased in IUGR placentas. Both mtDNA and NRF1 expression were instead significantly lower in their isolated cytotrophoblast cells. Finally, cytotrophoblast RCC activity was significantly increased in placentas of IUGR fetuses. No significant differences were found in PE placentas. This study sheds genuine new data into the complex physiology of placental oxygenation in IUGR fetuses. The higher mitochondrial content in IUGR placental tissue is reversed in cytotrophoblast cells, which instead present higher mitochondrial functionality. This suggests different mitochondrial content and activity depending on the placental cell lineage. Increased placental oxygen consumption might represent a limiting step in fetal growth restriction, preventing adequate oxygen delivery to the fetus.
• Keywords: Intrauterine growth restriction, Mitochondria, Placenta, Preeclampsia, Pregnancy
• O2k-Network Lab: IT Milan Clementi E
Labels: MiParea: Respiration, Patients
Organism: Human Tissue;cell: Genital Preparation: Intact cells, Permeabilized cells
Coupling state: ROUTINE, OXPHOS Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k