Effects of peroxisome proliferator-activated receptor gamma and its ligands on cytotrophoblast invasion in first trimester of pregnancy and mechanism thereof

Abstract

To investigate effects of peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands on cytotrophoblast invasion and its influence on matrix metalloproteinase (MMP)-2 and MMP-9 activities on cytotrophoblast cells. Samples of fresh placental trophoblast tissue were obtained from the pregnant women in first trimester. Cytotrophoblasts were isolated, cultured, and added with PPARgamma. Immunocytochemistry and inverted microscopy were used to examine the protein expression of PPARgamma in the cytotrophoblasts. Isolated cytotrophoblasts were inoculated in the Transwell chamber The natural stimulatory ligand of PPARgamma15-deoxy-delta (12, 14)-prostaglandin J2 (15d-PGJ2) and synthesized stimulatory ligand of PPARgamma troglitazone (TGZ) of the concentrations of 0, 1, and 10 micromol/L respectively were added respectively to examine the invasion ability of the cytotrophoblasts. Immunofluorochemistry and confocal technique and RT-PCR were used to examine the expression of MMP-2 and MMP-9. PPARgamma protein expression was detectable in the cytotrophoblasts, mainly in the nuclei. The invasion indexes of the cytotrophoblasts stimulated by 15d-PGJ2 and TGZ of different concentrations were significant lowered in a concentration-dependent manner, the effect of 15d-PGJ2 being stronger than that of TGZ (P < 0.05). After stimulated by 15d-PGJ2 and TGZ of different concentrations the mRNA expression and protein expression of MMP-9 and MMP-2 in the cytotrophoblasts were all inhibited significantly (all P < 0.05). PPARgamma plays an important role in the modulation of trophoblast invasion, and PPARgamma ligands can inhibit the trophoblast invasion through downregulating MMP-2 and MMP-9 expressions.