Preterm and infection-driven preterm labor: the role of peroxisome proliferator-activated receptors and retinoid X receptor.
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.
Holdsworth-Carson
Sarah J
SJ
Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Victoria, Australia.
Permezel
Michael
M
Rice
Greg E
GE
Lappas
Martha
M
D000328:Adult; D000650:Amnion / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D002821:Chorioamnionitis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D008297:Male; D007752:Obstetric Labor, Premature / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism*
D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D004247:DNA