Antioxidant defenses in the rat placenta in late gestation: increased labyrinthine expression of superoxide dismutases, glutathione peroxidase 3, and uncoupling protein 2.
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.
Jones
Megan L
ML
Schools of Anatomy & Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
Mark
Peter J
PJ
Lewis
Jessica L
JL
Mori
Trevor A
TA
Keelan
Jeffery A
JA
Waddell
Brendan J
BJ
D000818:Animals; D000975:Antioxidants / Q000032:analysis*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D020567:Fetal Weight; D015870:Gene Expression; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000235:genetics*; D006151:Guanosine / Q000031:analogs & derivatives / Q000032:analysis; D007473:Ion Channels / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology; D010920:Placenta / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D000071246:Uncoupling Protein 2
D000975:Antioxidants; D005938:Glucocorticoids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D006151:Guanosine; C046215:8-hydroxyguanosine; D003907:Dexamethasone; C505355:GPX3 protein, rat; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase