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

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.

Expression of angiogenic and neurotrophic factors in the human amnion and choriodecidua.

OBJECTIVE: Our objective was to identify the novel or differential expression of growth or development associated genes in the human gestational membranes that might play roles in pregnancy or in term or preterm parturition. STUDY DESIGN: Complementary DNA arrays were probed with [alpha(33)P]dCTP-labeled-complementary DNA that was prepared from the RNA of reflected amnion and choriodecidua that represent term not-in-labor, term spontaneous labor, and preterm labor with and without chorioamnionitis (n = 4 per group). Differential expression (term not-in-labor vs term spontaneous labor or preterm labor with chorioamnionitis vs preterm labor without chorioamnionitis) was evaluated by Wilcoxon tests. RESULTS: All 16 amnion samples expressed angiogenic factors (endothelin-2 and -3, vascular endothelial growth factor, and vascular endothelial growth factor-B) and neurotrophic factors (ephrin-A2, ephrin receptors-A2, -B1, -B3, -B4, and -B5, neuropilin-2, p75/nerve growth factor receptor and semaphorin-F). In both amnion and choriodecidua, the expression of vascular endothelial growth factor and the angiopoietin receptor, Tie-2, were greater with term spontaneous labor than with term not-in-labor (P <.05); increased VEGF receptor-2 (flk-1) expression was observed in term spontaneous labor choriodecidua (P <.05) but not amnion. Ephrin-A1 expression increased with term spontaneous labor in both tissues (P <.05). Semaphorin-F expression decreased with preterm labor with chorioamnionitis in choriodecidua (P <.05), although the trend was not significant in amnion (P =.1). CONCLUSION: Neurotrophic and angiogenic factor genes are expressed in amnion and choriodecidual membranes. Several of the genes exhibit differential expression with labor at term or in association with infection preterm, which suggests roles in or associated with these processes.