Abstract

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 J₂ (15d-PGJ₂)-induced luciferase activity, suggesting that 15d-PGJ₂ 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.