Peroxisome Proliferator-Activated Receptor Isoform Expression Changes in Human Gestational Tissues with Labor at Term

• Published in: Molecular pharmacology 2003-12, Vol.64 (6), p.1586-1590
• Main Authors: Berry, Elicia B E, Eykholt, Roberta, Helliwell, Rachel J A, Gilmour, R Stewart, Mitchell, Murray D, Marvin, Keith W
• Format: Article
• Language: English
• Subjects: Amnion - metabolism; Cell Line, Tumor; Female; Humans; Labor, Obstetric - metabolism; Placenta - metabolism; Pregnancy; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - genetics; Transcription Factors - biosynthesis; Transcription Factors - genetics
• ISSN: 0026-895X; 1521-0111
• DOI: 10.1124/mol.64.6.1586

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-α, -δ, and -γ. We have previously shown presence of PPAR-γ mRNA in the amnion, choriodecidua, and placenta, and its level of expression was unchanged with labor. To evaluate whether PPAR-α and -δ subtypes are present in intrauterine tissues, placentae were obtained from women at term after spontaneous vaginal delivery (TSL; n = 15) and elective caesarean section before labor (TNL; n = 15). Northern blot analyses were used to evaluate the mRNA for PPARs. Activities of PPARs were assessed using JEG3 choriocarcinoma cells transfected with a PPAR-response element reporter construct (pTK-PPREx3-luc) and treated with PPAR ligands. The PPAR-γ-specific ligand rosiglitazone induced PPAR response element (PPRE)-mediated activity in a concentration-dependent manner, whereas the PPAR-γ-specific irreversible inhibitor GW9662 fully inhibited this induction. However, GW9662 only partially inhibited 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 )-induced luciferase activity, suggesting that 15d-PGJ 2 may also activate either of the other isoforms. PPAR-α and -δ are expressed in the amnion, choriodecidua, and placental villous tissues. In the amnion, although for PPAR-α no significant difference in expression was observed with labor, PPAR-δ expression increased significantly ( p < 0.001). In the choriodecidua, expression of PPAR-α declined with labor ( p < 0.01), whereas, as in the amnion, PPAR-δ expression increased ( p < 0.05). In the placenta, both PPAR-α and -δ expression increased with labor ( p < 0.005). The changes observed with labor suggest that regulation of PPAR expression and function may have roles to the mechanisms that maintain pregnancy or initiate labor.