|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia 6009, Australia
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 µg/ml in drinking water; Days 1322, 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.
developmental biology, glucocorticoid receptor, placenta, pregnancy, syncytiotrophoblast
1 Supported by the National Health and Medical Research Council of Australia (Project Grant 254576).
2 Correspondence: Brendan J. Waddell, School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia. FAX: 61 8 6488 1051; bwaddell{at}anhb.uwa.edu.au
This article has been cited by other articles:
![]() |
A. E. Michael and A. T. Papageorghiou Potential significance of physiological and pharmacological glucocorticoids in early pregnancy Hum. Reprod. Update, September 1, 2008; 14(5): 497 - 517. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. P. Hewitt, P. J. Mark, and B. J. Waddell Glucocorticoids Prevent the Normal Increase in Placental Vascular Endothelial Growth Factor Expression and Placental Vascularity during Late Pregnancy in the Rat Endocrinology, December 1, 2006; 147(12): 5568 - 5574. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J. Mark and B. J. Waddell P-Glycoprotein Restricts Access of Cortisol and Dexamethasone to the Glucocorticoid Receptor in Placental BeWo Cells Endocrinology, November 1, 2006; 147(11): 5147 - 5152. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. P. Hewitt, P. J. Mark, A. M. Dharmarajan, and B. J. Waddell Placental Expression of Secreted Frizzled Related Protein-4 in the Rat and the Impact of Glucocorticoid-Induced Fetal and Placental Growth Restriction Biol Reprod, July 1, 2006; 75(1): 75 - 81. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |