Mitochondrial uncoupling protein 2 in the placenta may protect the preterm infant from increased reactive oxygen species following chorioamnionitis (#172)
In human pregnancy, a delicate balance exists between the production of reactive oxygen species (ROS) and anti-oxidant defences that protect the human placenta and fetus. The mitochondrial respiratory chain is the major source of ROS in most mammalian cells. Mitochondrial uncoupling protein 2 (UCP2) plays a critical role in the control of mitochondrial ROS production, and has also been implicated in regulating immune activity. Given that we have recently reported sex-specific alterations in placental ROS production in preterm neonates in response to antenatal betamethasone exposure, we aimed to examine placental UCP2 expression to elucidate mitochondrial processes that potentially contribute to poor perinatal outcomes in preterm infants.UCP2 mRNA expression was assessed in the placenta of very preterm (24-28 weeks; n=23), preterm (29-36 weeks; n=19) and term (37-41 weeks; n=11) neonates. Placental ROS production was assessed by measures of lipid peroxidation and nitrative stress in placental tissue homogenates. Arterial and venous cord blood TNFα levels were determined using ELISA. Histological chorioamnionitis was recorded from placental pathology reports following all preterm deliveries. Antenatal steroid administration, birth weight, infant sex and mode of delivery were recorded.: Placental UCP2 expression increased significantly with gestation (p=0.015) and was unaffected by infant sex or steroid exposure. Placental UCP2 expression was significantly reduced in small for gestational age (SGA) infants, irrespective of prematurity (p<0.05) and was decreased in pregnancies with choriomnionitis (p=0.006). UCP2 expression inversely correlated with arterial cord blood TNFα levels (r=-0.41), but had no relationship with measures of lipid peroxidation or nitrative stress. Exposure of the developing fetus to increased placental ROS is thought to contribute to the development of morbidities commonly associated with preterm birth. Our current data adds mechanistic support to this theory, with reduced placental UCP2 expression associated with chorioamnionitis, maternal inflammation (evidenced by increased maternal TNFα levels) and SGA deliveries in preterm neonates.