523. PLACENTAL ANTIOXIDANT ENZYMES IN RAT PREGNANCY SHOW ZONE- AND STAGE-DEPENDENT VARIATION

Abstract

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders including preeclampsia. Protection from oxidative stress is provided by antioxidant enzymes which inactivate reactive oxygen species (ROS). The rat placenta consists of two major zones, the junctional (JZ) and labyrinth (LZ), and because only the LZ grows in late gestation we hypothesized it generates more ROS and thus requires greater antioxidant protection. Our previous studies on expression of the antioxidants superoxide dismutase (SOD)-1, SOD-2 and catalase support this hypothesis. Here, we extend these observations to include mRNA expression of SOD-3 and thioredoxin reductases (Txnrd-1, -2, -3) and activities of SOD, hydrogen peroxide (H₂O₂) scavenging and xanthine oxidase (XO). Placental oxidative damage was assessed by measurement of F₂-isoprostanes and TBARS concentrations. We also measured the effects of maternal dexamethasone treatment, since glucocorticoid excess is known to induce oxidative damage in other tissues. Placentas were collected from untreated mothers on days 16 and 22 (term=day 23) and on day 22 after dexamethasone treatment from day 13 (1 μg/ml drinking water). SOD-3, Txnrd-1, -2, and -3 mRNAs were measured in JZ and LZ by qRT-PCR. F₂-isoprostanes were measured by GC-MS and kit assays were used to measure TBARS and the activities of SOD, H₂O₂ scavenging and XO. In both placental zones, expression of SOD-3 and Txnrd-1 mRNAs and H₂O₂ scavenging activity decreased from day 16 to 22, whereas XO activity increased. Dexamethasone treatment increased H₂O₂ scavenging in both zones, but had no effect on SOD or XO activities or antioxidant mRNA expression. Despite predicted increases in placental ROS generation in late pregnancy and after dexamethasone, neither F₂-isoprostanes nor TBARS were increased. These and our previous data suggest that endogenous protection against oxidative stress is abundant in the rat placenta and provides protection against potential oxidative insults including glucocorticoid excess.