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Accepted Preprint first posted online on 15 October 2009
Journal of Endocrinology (2009) In press
DOI: 10.1677/JOE-09-0321
© 2009 Society for Endocrinology
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RESEARCH

In response to oxidative stress, the expression of inflammatory cytokines and antioxidant enzymes are impaired in placenta, but not adipose tissue, of women with gestational diabetes

Martha Lappas, Amberlee Mitton and Michael Permezel

M Lappas, Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne, Australia
A Mitton, Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne, Australia
M Permezel, Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne, Australia

Correspondence: Martha Lappas, Email: mlappas{at}unimelb.edu.au

Objective: In response to oxidative stress, GDM placenta release less 8-isoprostane and TNF-{alpha}. The effect of oxidative stress on other cytokines and on antioxidant gene expression are unknown. The aim of this study was to further explore the antioxidant status and effect of oxidative stress in GDM tissue.

Design and methods: Human placenta, and subcutaneous and omental adipose tissue from women with and without GDM were exposed to hypoxanthine (HX)/xanthine oxidase (XO). Cytokine release was analysed by ELISA and cytokine and antioxidant gene expression by RT-PCR.

Results: Catalase and glutathione reductase (GR) mRNA expression was higher in GDM (n=18) compared to normal (n=23) placenta. There was no difference in glutathione peroxidase (GPx) and superoxide dismutase (SOD) mRNA expression. Antioxidant gene expression was unaltered between normal (n=18) and GDM (n=10) adipose tissue. HX/XO treatment significantly stimulated cytokine release (13/16 cytokines) and cytokine mRNA expression, and decreased antioxidant gene expression (catalase and GR) in human placenta from normal pregnant women. In GDM placenta, HX/XO only significantly increased the release of 3/16 cytokines, while there was no effect on antioxidant gene expression. In normal and GDM adipose tissues, HX/XO increased pro-inflammatory cytokine and 8-isoprostane release, while there was no change in antioxidant gene expression.

Conclusions: GDM placenta is characterised by increased antioxidant gene expression, and is less responsive to exogenous oxidative stress than tissues obtained from normal pregnant women. This may represent a protective or adaptive mechanism to prevent damage from further oxidative insult in utero as indicated by increased tissue antioxidant expression.







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