Peroxisome Proliferator-activated Receptors and Retinoid X Receptor-alpha in Term Human Gestational Tissues: Tissue Specific and Labour-associated Changes

Abstract Peroxisome proliferator-activated receptors (PPARs) and their transcriptional partner retinoid X receptor (RXR) are involved in transcriptionally regulating the events that contribute to the control of parturition in humans. Definitive data, however, are lacking with respect to PPAR and RXR expression and activation during term labour in human gestational tissues. The aim of this study, therefore, was to identify tissue and labour-associated changes of PPAR isoforms (α, δ and γ) and RXRα in placenta, amnion and choriodecidua. Gestational tissues from term non-labouring women were used for immunohistochemistry localisation and confirmation studies of PPAR isoforms (α, δ and γ) and RXRα. Human gestational tissues were then collected from term women not-in-labour (NIL) (elective Caesarean section), in-labour (IL) (emergency Caesarean section) and post-labour (PL) (normal vaginal delivery). Quantitative RT-PCR (qRT-PCR) and Western blotting were employed to study mRNA and protein expression profiles respectively. Significantly higher mRNA expression was observed in placental tissues taken from women in labour (PPARδ, PPARγ and RXRα). Elevated PPARδ and RXRα mRNA expression in fetal membranes was also associated with being in labour. In contrast, PPARγ mRNA in the amnion was decreased with term PL compared to NIL. In placenta, PPARα, PPARδ and PPARγ protein expression was significantly increased in the IL group compared to the NIL or PL group. There was no significant difference in PPAR or RXRα protein expression in both amnion and choriodecidua between the three labour groups. PPAR (α and γ) transcription factor DNA binding activity was found to decline IL compared to NIL and PL in the placenta. PPARδ DNA binding activity also decreased in the choriodecidua IL compared to PL. In amnion, PPARα DNA binding activity was found to be higher IL compared to NIL. In conclusion, term human labour is associated with changes in expression and activity of PPAR isoforms and its transcription partner, RXRα. This data is consistent with the hypothesis that PPAR:RXR are involved in regulating of the processes of human term parturition.