Peroxisome proliferator-activated receptor isoform expression changes in human gestational tissues with labor at term

Mol Pharmacol. 2003 Dec;64(6):1586-90. doi: 10.1124/mol.64.6.1586.

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-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amnion, choriodecidua, and placenta, and its level of expression was unchanged with labor. To evaluate whether PPAR-alpha and -delta 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-gamma-specific ligand rosiglitazone induced PPAR response element (PPRE)-mediated activity in a concentration-dependent manner, whereas the PPAR-gamma-specific irreversible inhibitor GW9662 fully inhibited this induction. However, GW9662 only partially inhibited 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)-induced luciferase activity, suggesting that 15d-PGJ2 may also activate either of the other isoforms. PPAR-alpha and -delta are expressed in the amnion, choriodecidua, and placental villous tissues. In the amnion, although for PPAR-alpha no significant difference in expression was observed with labor, PPAR-delta expression increased significantly (p < 0.001). In the choriodecidua, expression of PPAR-alpha declined with labor (p < 0.01), whereas, as in the amnion, PPAR-delta expression increased (p < 0.05). In the placenta, both PPAR-alpha and -delta 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Protein Isoforms
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors