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

Holdsworth-Carson, S.J.; Lim, R.; Mitton, A.; Whitehead, C.; Rice, G.E.; Permezel, M.; Lappas, M.

doi:10.1016/j.placenta.2009.12.009

« Previous Next »Placenta
Volume 31, Issue 3 , Pages 222-229, March 2010

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

S.J. Holdsworth-Carson
- Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia
- Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia
R. Lim
- Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia
- Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia
A. Mitton
- Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia
- Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia
C. Whitehead
- Department of Obstetrics and Gynaecology, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia
G.E. Rice
- Translational Proteomics, Baker IDI, Prahran, Victoria 3004, Australia
M. Permezel
- Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia
- Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia
M. Lappas
- Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia
- Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia
- Translational Proteomics, Baker IDI, Prahran, Victoria 3004, Australia
- Corresponding author. Department of Obstetrics and Gynaecology, University of Melbourne. Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Victoria 3084, Australia.

Accepted 8 December 2009. published online 04 January 2010.

Abstract

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 (RXRα), 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 IUGR, PE or co-existing PE and IUGR were compared to matched controls. Quantitative RT-PCR and Western blotting were used to examine mRNA and protein expression of PPARα, PPARδ, PPARγ and RXRα. DNA binding activity of PPAR isoforms were measured in nuclear protein extracts.

Results

GDM was associated with significantly lower placental PPARγ mRNA and protein, PPARα protein and RXRα 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 PPARα protein, PPARγ mRNA and protein and RXRα mRNA and protein expression. Significantly elevated protein expression of PPARα and RXRα were associated with IUGR placentae. IUGR and IUGR/PE placentae had significantly higher PPARγ DNA binding activity compared to controls.