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  • Title: [Effect of peroxisome proliferators-activated receptor gamma ligands on cytotrophoblast invasion in first trimester pregnancy].
    Author: Li SJ, Shang T, Chang ZQ, Li J, Li SY, Li QL, Rui GH.
    Journal: Zhonghua Fu Chan Ke Za Zhi; 2007 Aug; 42(8):518-22. PubMed ID: 17983488.
    Abstract:
    OBJECTIVE: To investigate the expression of peroxisome proliferators-activated receptor gamma (PPARgamma) in trophoblast and relation between PPARgamma ligands and trophoblast invasion. METHODS: We examined the expression of PPARgamma by immunohistochemistry, immunocytochemistry and real time quantitative PCR. We next examined, using the cytotrophoblast culture model, the biological role of PPARgamma ligands in vitro. RESULTS: PPARgamma was mainly localized in the nuclei of villous cytotrophoblast and extravillous cytotrophoblast of cell islands and cell columns. In villous tissue and cultured trophoblast from early first trimester, the level of expression of PPARgamma mRNA and protein was 36.0 +/- 5.1, 13.4 +/- 3.1 and 1.35 +/- 0.08, 1.13 +/- 0.11; from late first trimester it was 23.3 +/- 5.5, 6.1 +/- 1.3 and 1.17 +/- 0.03, 0.86 +/- 0.05, and the expression of PPARgamma was obviously decreased (P < 0.05). Our studies showed that both natural and synthetic PPARgamma agonists inhibited cytotrophoblast invasion in a concentration-dependent manner. In trophoblast from early and late first trimester, while 15-d-PGJ(2) at concentrations 1 and 10 micromol/L, troglitazone at a concentration 10 micromol/L, invasion index was 0.57 +/- 0.03, 0.43 +/- 0.02, 0.50 +/- 0.06 and 0.69 +/- 0.02, 0.59 +/- 0.03, 0.66 +/- 0.05. The effect on inhibition of trophoblast was significant compared with control (P < 0.05). Conversely, PPARgamma antagonists promoted cytotrophoblast invasion. Furthermore the PPARgamma antagonist abolished inhibitory effect of the PPARgamma agonists partially. PPARgamma ligands had a significant effect on cytotrophoblast from early first trimester more than cytotrophoblast from late first trimester (P < 0.05). CONCLUSIONS: PPARgamma plays an important role in the modulation of trophoblast invasion. Consequently, one can hypothesize that abnormal increases in the production of PPARgamma agonist ligands in placenta can alter trophoblast invasion and generate human pregnancy diseases such as preeclampsia.
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