Placental Expression of Peroxisome Proliferator-Activated Receptors in Rat Pregnancy and the Effect of Increased Glucocorticoid Exposure1

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Recent gene deletion studies indicate that PPARG and PPARD play critical roles in rodent development, including effects on placental vascularization. In this study we investigated the expression of the PPAR isoforms and their heterodimeric partner, RXRA, in the two functionally and morphologically distinct zones of the rat placenta during normal gestation and after glucocorticoid-induced fetal and placental growth restriction. Real-time reverse transcription-polymerase chain reaction and immunohistochemical analysis demonstrated markedly higher expression of Ppara, Pparg, and Rxra mRNA in labyrinth zone trophoblast as compared with basal zone near term. There was also a marked increase in Pparg (65%, P < 0.05) and Ppara (91%, P < 0.05) mRNA specifically in the labyrinth zone over the final third of pregnancy. In contrast, expression of Ppard mRNA fell (P < 0.001) in both placental zones over the same period. Maternal dexamethasone treatment (1 mug/ml in drinking water; Days 13-22, term = 23 days) reduced placental (44%) and fetal (31%) weights and resulted in a fall in Pparg (37%, P < 0.05) mRNA expression specifically in the labyrinth zone at Day 22. Placental expression of Ppara, Ppard, and Rxra was unaffected by dexamethasone treatment. These data suggest that PPARG:RXRA heterodimers play important roles in labyrinth zone growth late in pregnancy, possibly supporting vascular development. Moreover, glucocorticoid inhibition of placental growth appears to be mediated, in part, via a labyrinth-zone-specific suppression of PPARG.