Metabolic and oxidative phenotype of IUGR

Intrauterine Growth Restriction (IUGR) is a multifactorial disease of pregnancy that markedly increases perinatal mortal- ity and morbidity. In IUGR, the fetus fails to reach its growth potential. IUGR of placental origin without maternal clinical damage, and hypertensive disorders of pregnancy (HDP) associated with IUGR pregnancies share a common placental phenotype described as “placental insufficiency” that originates in early gestation, when the trophoblast invades the decidua. This process requires high availability of energy for cell growth, proliferation and metabolic activity. Mitochondria are the main energy producers in the cell. They consume oxygen (O2) and produce ATP by electron transport and oxidative phosphorylation taking place across the respiratory chain complexes located in the mitochondrial inner membrane. Mitochondrial alterations occur in several disorders, including malignant and benign proliferations and inflammatory conditions. The metabolic activity of the placenta is sustained throughout gestation by increasing mitochondrial activity and biogenesis. Damage to this process could lead to excessive generation of reactive oxygen and nitrogen species, contributing to the placental damage that has been shown in pathologies such as IUGR, HDP, gestational diabetes, and maternal obesity. We measured in IUGR and control pregnancies the mitochondrial (mt)DNA levels 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. The higher mitochondrial content in IUGR placental tissue is reversed in cytotrophoblast cells, which instead present higher mitochondrial functionality. This suggests different mitochon- drial 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.