Peroxisome proliferator-activated receptors are altered in pathologies of the human placenta: Gestational diabetes mellitus, intrauterine growth restriction and preeclampsia

Background. Common complications of pregnancy arise in part from dysfunctional placental development, and include gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Peroxisome proliferator-activated receptors (PPARs), and their partner retinoid X receptor a (RXR alpha), mediate trophoblast differentiation and thus may offer insight into the pathophysiology of these diseases Methods. Human placentae were obtained from women at term with GDM and were compared to uncomplicated term placentae Placentae from women who delivered preterm with ILJGR, PE or coexisting PE and IUGR were compared to matched controls. Quantitative RT-PCR and Western blotting were used to examine mRNA and protein expression of PPAR alpha, PPAR delta, PPAR gamma and RXRa DNA binding activity of PPAR isoforms were measured in nuclear protein extracts. Results GDM was associated with significantly lower placental PPAR gamma mRNA and protein, PPARa protein and RXR alpha. protein expression, while PPAR DNA binding activity remained unchanged Placentae from women with PE did not demonstrate any changes in mRNA or protein expression or PPAR DNA binding activity, while IUGR/PE placenta showed significant increases in PPARa. protein, PPAR gamma mRNA and protein and RXRa mRNA and protein expression. Significantly elevated protein expression of PPARa and RXRa were associated with IUGR placentae. IUGR and IUGR/PE placentae had significantly higher PPAR gamma DNA binding activity compared to controls Conclusions The data presented herein suggest that PPARs may be involved in the pathophysiology of GDM, PE and IUGR Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved