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.