This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yessoufou, A. Articles by Khan, N. A. Search for Related Content PubMed PubMed Citation Articles by Yessoufou, A. Articles by Khan, N. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information High Risk Pregnancy Pregnancy Loss

Peroxisome Proliferator-Activated Receptor Deficiency Increases the Risk of Maternal Abortion and Neonatal Mortality in Murine Pregnancy with or without Diabetes Mellitus: Modulation of T Cell Differentiation

Department of Physiology (A.Y., A.H., N.A.K.), University of Burgundy, Unité Propre de Recherche de l’Enseignement Supérieur Lipids and Nutrition, Faculty of Life Sciences, 21000 Dijon, France; Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l’Alimentation (P.B.), University of Burgundy, Dijon, France; and Laboratory of Cell Biology and Physiology (A.Y., K.M.), Faculty of Sciences and Techniques, University of Abomey-Calavi, 01BP 526 Cotonou, Bénin

Address all correspondence and requests for reprints to: Prof. Naim Akhtar Khan, Head, Department of Physiology, Unité Propre de Recherche de l’Enseignement Supérieur Lipides and Nutrition, Université de Bourgogne, Faculté des Sciences de la vie, 6 Boulevard Gabriel, 21000 Dijon, France. E-mail: Naim.Khan{at}u-bourgogne.fr.

We assessed the implication of peroxisome proliferator-activated receptor (PPAR) deficiency in pregnancy outcome and neonatal survival and in the modulation of T cell differentiation in murine diabetic pregnancy and their offspring. Pregnant wild-type (WT) and PPAR-null mice of C57BL/6J genetic background were rendered diabetic by five low doses of streptozotocin. We observed that, in the absence of diabetes, PPAR deficiency resulted in an increase in abortion rate, i.e. 0% in WT mice vs. 20% in PPAR-null mice [odds ratio (OR) = 14.33; P = 0.013]. Under diabetic conditions, the abortion rate was enhanced, i.e. 8.3% in WT mice vs. 50% in PPAR-null mice (OR = 4.28; P = 0.011). In the pups born to diabetic dams, the offspring mortality, due to the absence of PPAR, was enhanced, i.e. 27.7% in WT mice vs. 78.9% in PPAR-null animals (OR = 11.48; P < 0.001). Moreover, we observed that T helper (Th) 1/Th2 balance was shifted to a pregnancy protecting Th2 phenotype in WT diabetic dams and to a noxious Th1 phenotype in PPAR-null mice with diabetic pregnancy. Furthermore, offspring born to diabetic WT dams were hyperinsulinemic and hyperglycemic, and they exhibited up-regulated profile of Th2 cytokines, whereas those born to diabetic PPAR-null dams were hypoinsulinemic and hyperglycemic, and they showed down-regulated profile of Th2 cytokines. However, IFN-, a Th1 cytokine, was up-regulated in the offspring of both diabetic WT and PPAR-null dams. Altogether, our results suggest that PPAR deficiency in mice may be implicated in the increase in maternal abortion, neonatal mortality, and T cell differentiation.

This article has been cited by other articles:

				N Martinez, E Capobianco, V White, M C Pustovrh, R Higa, and A Jawerbaum Peroxisome proliferator-activated receptor {alpha} activation regulates lipid metabolism in the feto-placental unit from diabetic rats Reproduction, July 1, 2008; 136(1): 95 - 103. [Abstract] [Full Text] [PDF]

				J.-M. Ategbo, O. Grissa, A. Yessoufou, A. Hichami, K. L. Dramane, K. Moutairou, A. Miled, A. Grissa, M. Jerbi, Z. Tabka, et al. Modulation of Adipokines and Cytokines in Gestational Diabetes and Macrosomia J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4137 - 4143. [Abstract] [Full Text] [PDF]