Ligand-activated peroxisome proliferator activated receptor gamma alters placental morphology and placental fatty acid uptake in mice.
The nuclear receptor peroxisome proliferator activated receptor gamma (PPARgamma) is essential for murine placental development. We previously showed that activation of PPARgamma in primary human trophoblasts enhances the uptake of fatty acids and alters the expression of several proteins associated with fatty acid trafficking. In this study we examined the effect of ligand-activated PPARgamma on placental development and transplacental fatty acid transport in wild-type (wt) and PPARgamma(+/-) embryos. We found that exposure of pregnant mice to the PPARgamma agonist rosiglitazone for 8 d (embryonic d 10.5-18.5) reduced the weights of wt, but not PPARgamma(+/-) placentas and embryos. Exposure to rosiglitazone reduced the thickness of the spongiotrophoblast layer and the surface area of labyrinthine vasculature, and altered expression of proteins implicated in placental development. The expression of fatty acid transport protein 1 (FATP1), FATP4, adipose differentiation related protein, S3-12, and myocardial lipid droplet protein was enhanced in placentas of rosiglitazone-treated wt embryos, whereas the expression of FATP-2, -3, and -6 was decreased. Additionally, rosiglitazone treatment was associated with enhanced accumulation of the fatty acid analog 15-(p-iodophenyl)-3-(R, S)-methyl pentadecanoic acid in the placenta, but not in the embryos. These results demonstrate that in vivo activation of PPARgamma modulates placental morphology and fatty acid accumulation.
Schaiff
W Timothy
WT
Washington University School of Medicine, Department of Obstetrics and Gynecology, Campus Box 8064, 4566 Scott Avenue, St. Louis, Missouri 63110, USA.
Knapp
F F Russ
FF
Barak
Yaacov
Y
Biron-Shental
Tal
T
Nelson
D Michael
DM
Sadovsky
Yoel
Y
D000818:Animals; D005227:Fatty Acids / Q000493:pharmacokinetics*; D005260:Female; D020567:Fetal Weight / Q000187:drug effects / Q000502:physiology; D005838:Genotype; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C049338:iodofiltic acid