Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 21

Abstract

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F(2)-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.

Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant capacity but does not protect against fetal growth restriction induced by placental ischaemia–reperfusion injury

“…In this study, we show that expression and activity of antioxidant enzymes increase towards term, confirming our previous report in chow-fed animals (Jones et al 2010). This is consistent with an up-regulation of placental antioxidant defences as placental oxygenation increases, which occurs on two occasions during normal gestation: following the rapid onset of maternal intraplacental circulation (10-12 weeks human gestation (Myatt & Cui 2004)) and during late gestation when fetal demand is maximal (Takehara et al 1990, Perkins 2006.…”

“…As such, it is perhaps unsurprising that antioxidant responses differ between the two placental zones in late gestation, and this highlights the need to consider these zones separately in rodent studies. The majority of antioxidant enzymes were more highly expressed in the placental LZ than in the JZ, the single exception being Gpx3 expression, which was considerably higher in JZ, and this is consistent with our previous findings in chow-fed animals (Jones et al 2010). Overall, the placental LZ appeared to exhibit enhanced antioxidant defences compared with the JZ.…”

“…Fetal weight of the contralateral horn was unaffected by UAO irrespective of maternal diet. In Sham-treated animals, placental weight increased with maternal Hn3 diet (9%, P!0.05), again Omega-3 fatty acids and placental antioxidants consistent with untreated pregnancy (Jones et al 2010). In UAO-treated mothers, total placental weight was unaffected in both diet groups, although LZ weight was reduced in both occluded (7.9-11.3%, P!0.01) and contralateral horns (2.5-10.9%; overall P!0.05, pooled diet groups); JZ weight was unaffected by UAO.…”

“…Placental ROS generation is high due to the high metabolic activity of placental cells (Myatt & Cui 2004), and so all major antioxidant systems are present within the placenta (Myatt & Cui 2004, Perkins 2006, Jones et al 2010. Several placenta-related disorders such as pre-eclampsia (PE), intrauterine growth restriction (IUGR), miscarriage, and gestational diabetes mellitus are characterized by increased placental oxidative stress (Coughlan et al 2004, Biri et al 2006, Jauniaux et al 2006, Myatt 2010).…”

Maternal dietary omega-3 fatty acids and placental function

“…Placental ROS generation is high due to the high inherent metabolic activity of the placental cells; therefore all major antioxidant systems are present within the placenta (Perkins 2006, Jones et al 2010.…”