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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 10 3808-3814
Copyright © 2000 by The Endocrine Society

Original Studies

Placental Peroxisome Proliferator-Activated Receptor-{gamma} Is Up-Regulated by Pregnancy Serum1

Leslie L. Waite, Eric C. Person, Yan Zhou, Kee-Hak Lim, Thomas S. Scanlan and Robert N. Taylor

Departments of Obstetrics, Gynecology, and Reproductive Sciences (L.L.W., R.N.T.), Pharmaceutical Chemistry and Cellular and Molecular Pharmacology (T.S.S.), Stomatology (Y.Z.), and Graduate Program in Biophysics (E.C.P.), University of California, San Francisco, California 94143; and Department of Obstetrics and Gynecology, Harvard Beth Israel-Deaconess Hospital (K.-H.L.), Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Dr. Leslie L. Waite, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California 94143.

Lipid metabolism plays an important role in normal pregnancy adaptation and in pathological pregnancy (e.g. preeclampsia). In the current studies we examined the expression of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) in tissues and cells relevant to human pregnancy. We found that PPAR{gamma} is expressed in placental cytotrophoblasts in vivo and in trophoblasts (primary and choriocarcinoma cells) and fetal endothelial cells in vitro. We characterized primary cytotrophoblasts and two cell lines with which to study PPAR{gamma} regulation in human pregnancy. Like primary cytotrophoblasts, the choriocarcinoma cell line JEG-3 has endogenous PPAR{gamma} expression. Normal positive and negative PPAR{gamma} regulation was observed in the latter cells. We also created a new JEG-3-derived cell line (EP-JEG) by stable insertion of a PPAR response element-luciferase reporter gene construct. Together, these cell lines are useful for studying PPAR{gamma} expression and activation in human trophoblasts. We examined PPAR{gamma} regulation in these cells by human serum and found that PPAR{gamma} protein expression and activation are dramatically increased by sera from pregnant women. Preliminary characterization of the regulatory principle(s) is consistent with a prostanoid or fatty acid derivative. The results suggest that increased activation of PPAR{gamma} may play an important role in maternal metabolism during human pregnancy.




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