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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Li
Shu-Juan
SJ
Department of Obstetrics and Gynecology, Second Affiliated Hospital, China Medical University, Shenyang 110004, China.
Shang
Tao
T
Li
Si-yang
SY
Li
Qiu-ling
QL
D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D047495:PPAR gamma / Q000096:biosynthesis / Q000494:pharmacology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C477819:15-deoxyprostaglandin J2; D002839:Chromans; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077288:Troglitazone; D015230:Prostaglandin D2