Increased trophoblast oxygen consumption in IUGR

BACKGROUND We have previously shown that IntraUterine Growth Restriction (IUGR), is characterized by higher placental mitochondrial (mt) DNA levels than controls (C), and that this increase is negatively related with umbilical venous oxygenation. Here, we evaluate mt oxygen (O2) consumption and respiratory chain complexes (RCC) gene expression, in trophoblast cells isolated from IUGR and preeclamptic (PE) placentas. METHODS Cytotrophoblast cells were isolated from 16 placentas (8 IUGR, 3 PE alone, 5 C) of non-smoking women at elective caesarean section, and characterized by cytofluorimetry using cytokeratin-7 and anti-vimentin antibodies. mRNA levels of NDUFA9 (CI), ETFDH (CII), UQCRC1 (CIII) and COX4I1 (CIV) were quantified by Real Time (RT) PCR. O2 consumption was evaluated by High Resolution Respirometry (HRR), by administration of substrates and inhibitors of different RCC, thus allowing the measure of the global cell and of single complexes activity. Data were normalized by mtDNA content. RESULTS IUGR presented significantly lower UQCRC1 and COX4I1 mRNA levels than C (p<0.05). On the contrary, both raw (figure 1A) and normalized data (figure 1B) in IUGR with or without PE (but not in PE without IUGR) showed significantly higher O2 consumption levels of RCC, altogether and singularly, vs C (p<0.05 and p<0.01), particularly for CIV. In the entire population most of HRR data negatively related with ga and with placental and fetal weights. DISCUSSION Our data show lower mRNA levels of CIII and CIV subunits in trophoblast cells from insufficient placentas of IUGR fetuses, in contrast with the RCC higher functionality, suggesting a compensatory mechanism to their lower expression. These results shed new light into placental oxygenation in IUGR, suggesting that increased placental oxygen utilization may represent a limiting step in fetal growth restriction.