title: Peroxisome proliferator-activated receptor isoform expression changes in human gestational tissues with labor at term.
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.
authors.affiliation: The Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand. ebe.berry@auckland.ac.nz
authors.forename: Elicia B E
authors.initials: EB
authors.lastname: Berry
authors.forename: Roberta
authors.initials: R
authors.lastname: Eykholt
authors.forename: Rachel J A
authors.initials: RJ
authors.lastname: Helliwell
authors.forename: R Stewart
authors.initials: RS
authors.lastname: Gilmour
authors.forename: Murray D
authors.initials: MD
authors.lastname: Mitchell
authors.forename: Keith W
authors.initials: KW
authors.lastname: Marvin
mesh_terms: D000650:Amnion / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors