TY - JOUR
T1 - Ligand-activated peroxisome proliferator activated receptor γ alters placental morphology and placental fatty acid uptake in mice
AU - Schaiff, W. Timothy
AU - Knapp, F. F.
AU - Barak, Yaacov
AU - Biron-Shental, Tal
AU - Nelson, D. Michael
AU - Sadovsky, Yoel
PY - 2007/8
Y1 - 2007/8
N2 - The nuclear receptor peroxisome proliferator activated receptor γ (PPARγ) is essential for murine placental development. We previously showed that activation of PPARγ 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 PPARγ on placental development and transplacental fatty acid transport in wild-type (wt) and PPARγ+/- embryos. We found that exposure of pregnant mice to the PPARγ agonist rosiglitazone for 8 d (embryonic d 10.5-18.5) reduced the weights of wt, but not PPARγ +/- 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-(piodophenyl)-3-(R, S)-methyl pentadecanoic acid in the placenta, but not in the embryos. These results demonstrate that in vivo activation of PPARγ modulates placental morphology and fatty acid accumulation.
AB - The nuclear receptor peroxisome proliferator activated receptor γ (PPARγ) is essential for murine placental development. We previously showed that activation of PPARγ 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 PPARγ on placental development and transplacental fatty acid transport in wild-type (wt) and PPARγ+/- embryos. We found that exposure of pregnant mice to the PPARγ agonist rosiglitazone for 8 d (embryonic d 10.5-18.5) reduced the weights of wt, but not PPARγ +/- 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-(piodophenyl)-3-(R, S)-methyl pentadecanoic acid in the placenta, but not in the embryos. These results demonstrate that in vivo activation of PPARγ modulates placental morphology and fatty acid accumulation.
UR - http://www.scopus.com/inward/record.url?scp=34547121969&partnerID=8YFLogxK
U2 - 10.1210/en.2007-0211
DO - 10.1210/en.2007-0211
M3 - Article
C2 - 17463056
AN - SCOPUS:34547121969
SN - 0013-7227
VL - 148
SP - 3625
EP - 3634
JO - Endocrinology
JF - Endocrinology
IS - 8
ER -