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

Faculty of Medical and Health Sciences, The Liggins Institute, University of Auckland, Auckland, New Zealand

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-, -, and -. We have previously shown presence of PPAR- mRNA in the amnion, choriodecidua, and placenta, and its level of expression was unchanged with labor. To evaluate whether PPAR- and - 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--specific ligand rosiglitazone induced PPAR response element (PPRE)-mediated activity in a concentration-dependent manner, whereas the PPAR--specific irreversible inhibitor GW9662 fully inhibited this induction. However, GW9662 only partially inhibited 15-deoxy-^12,14-prostaglandin J₂ (15d-PGJ₂)-induced luciferase activity, suggesting that 15d-PGJ₂ may also activate either of the other isoforms. PPAR- and - are expressed in the amnion, choriodecidua, and placental villous tissues. In the amnion, although for PPAR- no significant difference in expression was observed with labor, PPAR- expression increased significantly (p < 0.001). In the choriodecidua, expression of PPAR- declined with labor (p < 0.01), whereas, as in the amnion, PPAR- expression increased (p < 0.05). In the placenta, both PPAR- and - 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.

Address correspondence to: Elicia Berry, The Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: ebe.berry{at}auckland.ac.nz

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