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Title: | Peroxisome proliferator-activated receptors are altered in pathologies of the human placenta: Gestational diabetes mellitus, intrauterine growth restriction and preeclampsia. | Authors: | Lim R.;Mitton A.;Whitehead C.;Holdsworth-Carson S.J.;Rice G.E.;Permezel M.;Lappas M. | Institution: | (Holdsworth-Carson, Lim, Mitton, Permezel, Lappas) Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Vic. 3084, Australia (Holdsworth-Carson, Lim, Mitton, Permezel, Lappas) Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic. 3084, Australia (Whitehead) Department of Obstetrics and Gynaecology, Monash Medical Centre, Monash University, Clayton, Vic. 3168, Australia (Rice, Lappas) Translational Proteomics, Baker IDI, Prahran, Vic. 3004, Australia | Issue Date: | 10-Oct-2012 | Copyright year: | 2010 | Publisher: | W.B. Saunders Ltd (32 Jamestown Road, London NW1 7BY, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Placenta. 31 (3) (pp 222-229), 2010. Date of Publication: March 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 (RXRalpha), mediate trophoblast differentiation and thus may offer insight into the pathophysiology of these diseases. Method(s): 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 PPARalpha, PPARdelta, PPARgamma and RXRalpha. DNA binding activity of PPAR isoforms were measured in nuclear protein extracts. Result(s): GDM was associated with significantly lower placental PPARgamma mRNA and protein, PPARalpha protein and RXRalpha 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 PPARalpha protein, PPARgamma mRNA and protein and RXRalpha mRNA and protein expression. Significantly elevated protein expression of PPARalpha and RXRalpha were associated with IUGR placentae. IUGR and IUGR/PE placentae had significantly higher PPARgamma DNA binding activity compared to controls. Conclusion(s): The data presented herein suggest that PPARs may be involved in the pathophysiology of GDM, PE and IUGR. Crown Copyright © 2009. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.placenta.2009.12.009 | PubMed URL: | 20045185 [http://www.ncbi.nlm.nih.gov/pubmed/?term=20045185] | ISSN: | 0143-4004 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/31015 | Type: | Article | Subjects: | *peroxisome proliferator activated receptor/ec [Endogenous Compound] peroxisome proliferator activated receptor alpha/ec [Endogenous Compound] peroxisome proliferator activated receptor delta/ec [Endogenous Compound] peroxisome proliferator activated receptor gamma/ec [Endogenous Compound] retinoid X receptor alpha/ec [Endogenous Compound] *preeclampsia/et [Etiology] article DNA binding gene expression human human tissue *intrauterine growth retardation/co [Complication] *intrauterine growth retardation/et [Etiology] *placenta *preeclampsia/co [Complication] pregnancy pregnancy complication/co [Complication] *pregnancy diabetes mellitus/co [Complication] *pregnancy diabetes mellitus/et [Etiology] priority journal protein expression reverse transcription polymerase chain reaction Western blotting DNA/ec [Endogenous Compound] messenger RNA/ec [Endogenous Compound] *pregnancy diabetes mellitus / *complication / *etiology priority journal protein expression reverse transcription polymerase chain reaction Western blotting DNA binding article gene expression human human tissue *intrauterine growth retardation / *complication / *etiology *placenta *preeclampsia / *complication / *etiology pregnancy pregnancy complication / complication |
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