[Effect of peroxisome proliferators-activated receptor gamma ligands on cytotrophoblast invasion in first trimester pregnancy].
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.
Li
Shu-juan
SJ
Department of Obstetrics and Gynecology, Second Affiliated Hospital of China Medical University, Shenyang 110004, China.
Shang
Tao
T
Chang
Zi-qiang
ZQ
Li
Jun
J
Li
Si-yang
SY
Li
Qiu-ling
QL
Rui
Guang-hai
GH
D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; 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; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077288:Troglitazone; D015230:Prostaglandin D2