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Reproduction (2009) 137 1007-1015
DOI: 10.1530/REP-08-0496
Copyright © 2009 Society for Reproduction and Fertility
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RESEARCH

Preterm and infection-driven preterm labor: the role of peroxisome proliferator-activated receptors and retinoid X receptor

Sarah J Holdsworth-Carson1,2, Michael Permezel1,2, Greg E Rice3 and Martha Lappas1,2

1 Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia2 Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia3 Translational Proteomics, Baker IDI, Melbourne, Victoria 3004, Australia

Correspondence should be addressed to M Lappas at Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne; Email: mlappas{at}unimelb.edu.au

Approximately 8% of births are complicated by preterm delivery. To improve neonatal outcomes, a greater understanding of the mechanisms surrounding preterm parturition is required. Peroxisome proliferator-activated receptors (PPARs) have been implicated in the regulation of labor at term where they exhibit anti-inflammatory properties. Thus, we hypothesize that dysregulation of PPAR expression and activity may be associated with preterm labor and infection-associated preterm labor. The aim of this study was to compare the expression and activity of PPARs and the expression of retinoid X-receptor {alpha} (RXRA) in gestational tissues from term and preterm deliveries, and from infection-associated preterm deliveries. Quantitative RT-PCR, western blotting and activity ELISA were used to study expression and DNA binding profiles. Compared with term, preterm parturition was associated with an increased expression of PPAR {delta} (PPARD; mRNA and protein), PPAR {gamma} (PPARG; protein) and RXRA (protein) in the placenta and PPARD (mRNA and protein) and RXRA (mRNA) in the choriodecidua. There was, however, no change in preterm PPAR DNA binding activity compared with term. Preterm chorioamnionitis (CAM) demonstrated protein degradation in the choriodecidua and was associated with a decline in the mRNA expression of PPAR {alpha} (PPARA) and RXRA compared with uninfected preterm cases. PPAR DNA binding activity increased in the placenta (PPARD and PPARG) and decreased in the amnion (PPARA and PPARG) in association with preterm CAM. In conclusion, idiopathic preterm deliveries were associated with an increase in PPAR:RXR expression and preterm CAM was associated with a decrease in PPAR:RXR expression and tissue-specific alterations in transcriptional activity. The reasons for such dysregulation remain to be determined; however, the data are consistent with the hypothesis that PPARs may play a role in preterm labor and infection-complicated preterm deliveries.







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