Diabetes 52:2951-2958, 2003
© 2003 by the American Diabetes Association, Inc.
Gestational Diabetes Induces Placental Genes for Chronic Stress and Inflammatory Pathways
Tatjana Radaelli,
Ali Varastehpour,
Patrick Catalano, and
Sylvie Hauguel-de Mouzon
From the Department of Reproductive Biology, Schwartz Center for Metabolism and Nutrition, University School of Medicine at MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio
A physiological state of insulin resistance is required to preferentially direct maternal nutrients toward the feto-placental unit, allowing adequate growth of the fetus. When women develop gestational diabetes mellitus (GDM), insulin resistance is more severe and disrupts the intrauterine milieu, resulting in accelerated fetal development with increased risk of macrosomia. As a natural interface between mother and fetus, the placenta is the obligatory target of such environmental changes. However, the molecular basis for the imbalance that leads to fetal, neonatal, and adult metabolic compromises is not well understood. We report that GDM elicits major changes in the expression profile of placental genes with a prominent increase in markers and mediators of inflammation. Within the 435 transcripts reproducibly modified, genes for stress-activated and inflammatory responses represented the largest functional cluster (18.5% of regulated genes). Upregulation of interleukins, leptin, and tumor necrosis factor- receptors and their downstream molecular adaptors indicated an activation of pathways recruiting stress-activated protein/c-Jun NH2-terminal kinases. Transcriptional activation of extracellular matrix components and angiogenic activators pointed to a major structural reorganization of the placenta. Thus, placental transcriptome emerges as a primary target of the altered environment of diabetic pregnancy. The genes identified provide the basis to elucidate links between inflammatory pathways and GDM-associated insulin resistance.
Address correspondence and reprint requests to Dr. Sylvie Hauguel-de Mouzon, Department of Obstetrics, 2500 MetroHealth Dr., Cleveland, OH 44109. E-mail: sdemouzon{at}aol.com

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Copyright © 2003 by the American Diabetes Association.
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