Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2013, Article ID 970276, 8 pages
http://dx.doi.org/10.1155/2013/970276
Review Article

The Role of PPARs in Placental Immunology: A Systematic Review of the Literature

Department of Gynecology and Obstetrics, Ludwig Maximilians University of Munich, Maistraße 11, 80337 Munich, Germany

Received 30 November 2012; Accepted 18 February 2013

Academic Editor: Regina Ensenauer

Copyright © 2013 Stefan Hutter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. J. Renaud, L. M. Postovit, S. K. Macdonald-Goodfellow, G. T. McDonald, J. D. Caldwell, and C. H. Graham, “Activated macrophages inhibit human cytotrophoblast invasiveness in vitro,” Biology of Reproduction, vol. 73, no. 2, pp. 237–243, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. F. Reister, H. G. Frank, J. C. P. Kingdom et al., “Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women,” Laboratory Investigation, vol. 81, no. 8, pp. 1143–1152, 2001. View at Google Scholar · View at Scopus
  3. S. E. Hiby, J. J. Walker, K. M. O'Shaughnessy et al., “Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success,” Journal of Experimental Medicine, vol. 200, no. 8, pp. 957–965, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. P. J. Williams, J. N. Bulmer, R. F. Searle, B. A. Innes, and S. C. Robson, “Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy,” Reproduction, vol. 138, no. 1, pp. 177–184, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. T. G. Wegmann, H. Lin, L. Guilbert, and T. R. Mosmann, “Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?” Immunology Today, vol. 14, no. 7, pp. 353–356, 1993. View at Google Scholar · View at Scopus
  6. S. A. McCracken, E. Gallery, and J. M. Morris, “Pregnancy-specific down-regulation of NF-kappa B expression in T cells in humans is essential for the maintenance of the cytokine profile required for pregnancy success,” The Journal of Immunology, vol. 172, no. 7, pp. 4583–4591, 2004. View at Google Scholar · View at Scopus
  7. Y. Sasaki, D. Darmochwal-Kolarz, D. Suzuki et al., “Proportion of peripheral blood and decidual CD4+CD25bright regulatory T cells in pre-eclampsia,” Clinical and Experimental Immunology, vol. 149, no. 1, pp. 139–145, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. T. Tilburgs, D. L. Roelen, B. J. Van Der Mast et al., “Evidence for a selective migration of fetus-specific CD4+CD25bright regulatory T cells from the peripheral blood to the decidua in human pregnancy,” The Journal of Immunology, vol. 180, no. 8, pp. 5737–5745, 2008. View at Google Scholar · View at Scopus
  9. S. Guenther, T. Vrekoussis, S. Heublein et al., “Decidual macrophages are significantly increased in spontaneous miscarriages and over-express fasL: a potential role for macrophages in trophoblast apoptosis,” International Journal of Molecular Sciences, vol. 13, no. 7, pp. 9069–9080, 2012. View at Google Scholar
  10. R. K. Semple, V. K. K. Chatterjee, and S. O'Rahilly, “PPARγ and human metabolic disease,” The Journal of Clinical Investigation, vol. 116, no. 3, pp. 581–589, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Yu and J. K. Reddy, “Transcription coactivators for peroxisome proliferator-activated receptors,” Biochimica et Biophysica Acta, vol. 1771, no. 8, pp. 936–951, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. S. W. Beaven and P. Tontonoz, “Nuclear receptors in lipid metabolism: targeting the heart of dyslipidemia,” Annual Review of Medicine, vol. 57, pp. 313–329, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. G. Chinetti, J. C. Fruchart, and B. Staels, “Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation,” Inflammation Research, vol. 49, no. 10, pp. 497–505, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. T. J. Standiford, V. G. Keshamouni, and R. C. Reddy, “Peroxisome proliferator-activated receptor-{gamma} as a regulator of lung inflammation and repair,” Proceedings of the American Thoracic Society, vol. 2, pp. 226–231, 2005. View at Google Scholar
  15. L. Michalik, B. Desvergne, C. Dreyer, M. Gavillet, R. N. Laurini, and W. Wahli, “PPAR expression and function during vertebrate development,” International Journal of Developmental Biology, vol. 46, no. 1, pp. 105–114, 2002. View at Google Scholar · View at Scopus
  16. M. Lappas and G. E. Rice, “Transcriptional regulation of the processes of human labour and delivery,” Placenta, vol. 30, supplement, pp. 90–95, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. S. J. Holdsworth-Carson, R. Lim, A. Mitton et al., “Peroxisome proliferator-activated receptors are altered in pathologies of the human placenta: gestational diabetes mellitus, intrauterine growth restriction and preeclampsia,” Placenta, vol. 31, no. 3, pp. 222–229, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Tarrade, K. Schoonjans, L. Pavan et al., “PPARγ/RXRα heterodimers control human trophoblast invasion,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 5017–5024, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. N. Martínez, M. Kurtz, E. Capobianco, R. Higa, V. White, and A. Jawerbaum, “PPARα agonists regulate lipid metabolism and nitric oxide production and prevent placental overgrowth in term placentas from diabetic rats,” Journal of Molecular Endocrinology, vol. 47, no. 1, pp. 1–12, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. H. Wang, H. Xie, X. Sun et al., “Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor δ signaling is critical to pregnancy success,” The Journal of Biological Chemistry, vol. 282, no. 52, pp. 37770–37782, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Tarrade, K. Schoonjans, L. Pavan et al., “PPARγ/RXRα heterodimers control human trophoblast invasion,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 5017–5024, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. B. Rauwel, B. Mariamé, H. Martin et al., “Activation of peroxisome proliferator-activated receptor gamma by human cytomegalovirus for De Novo replication impairs migration and invasiveness of cytotrophoblasts from early placentas,” Journal of Virology, vol. 84, no. 6, pp. 2946–2954, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Belfort, R. Berria, J. Cornell, and K. Cusi, “Fenofibrate reduces systemic inflammation markers independent of its effects on lipid and glucose metabolism in patients with the metabolic syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 2, pp. 829–836, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. P. Lefebvre, G. Chinetti, J. C. Fruchart, and B. Staels, “Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis,” The Journal of Clinical Investigation, vol. 116, pp. 571–580, 2006. View at Publisher · View at Google Scholar
  25. Q. Wang, H. Fujii, and G. T. Knipp, “Expression of PPAR and RXR isoforms in the developing rat and human term placentas,” Placenta, vol. 23, no. 8-9, pp. 661–671, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. N. Martínez, M. Kurtz, E. Capobianco, R. Higa, V. White, and A. Jawerbaum, “PPARα agonists regulate lipid metabolism and nitric oxide production and prevent placental overgrowth in term placentas from diabetic rats,” Journal of Molecular Endocrinology, vol. 47, no. 1, pp. 1–12, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. L. G. Mikael, J. Pancer, Q. Wu, and R. Rozen, “Disturbed one-carbon metabolism causing adverse reproductive outcomes in mice is associated with altered expression of apolipoprotein AI and inflammatory mediators PPARα, interferon-γ, and interleukin-10,” Journal of Nutrition, vol. 142, no. 3, pp. 411–418, 2012. View at Google Scholar
  28. A. Yessoufou, A. Hichami, P. Besnard, K. Moutairou, and N. A. Khan, “Peroxisome proliferator-activated receptor α deficiency increases the risk of maternal abortion and neonatal mortality in murine pregnancy with or without diabetes mellitus: modulation of T cell differentiation,” Endocrinology, vol. 147, no. 9, pp. 4410–4418, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Mukherjee, L. Jow, G. E. Croston, and J. R. Paterniti, “Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARγ2 versus PPARγ1 and activation with retinoid X receptor agonists and antagonists,” The Journal of Biological Chemistry, vol. 272, no. 12, pp. 8071–8076, 1997. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Wang, H. Xie, X. Sun et al., “Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor δ signaling is critical to pregnancy success,” The Journal of Biological Chemistry, vol. 282, no. 52, pp. 37770–37782, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. Y. Barak, D. Liao, W. He et al., “Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 1, pp. 303–308, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Julan, H. Guan, J. P. Van Beek, and K. Yang, “Peroxisome proliferator-activated receptor δ suppresses 11β-hydroxysteroid dehydrogenase type 2 gene expression in human placental trophoblast cells,” Endocrinology, vol. 146, no. 3, pp. 1482–1490, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. S. E. Dunn, R. Bhat, D. S. Straus et al., “Peroxisome proliferator-activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity,” Journal of Experimental Medicine, vol. 207, no. 8, pp. 1599–1608, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. B. Toth, M. Bastug, C. Scholz et al., “Leptin and peroxisome proliferator-activated receptors: impact on normal and disturbed first trimester human pregnancy,” Histology and Histopathology, vol. 23, no. 12, pp. 1465–1475, 2008. View at Google Scholar · View at Scopus
  35. W. T. Schaiff, F. F. Knapp, Y. Barak, T. Biron-Shental, D. M. Nelson, and Y. Sadovsky, “Ligand-activated peroxisome proliferator activated receptor γ alters placental morphology and placental fatty acid uptake in mice,” Endocrinology, vol. 148, no. 8, pp. 3625–3634, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Tarrade, K. Schoonjans, L. Pavan et al., “PPARγ/RXRα heterodimers control human trophoblast invasion,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 5017–5024, 2001. View at Publisher · View at Google Scholar · View at Scopus
  37. F. P. McCarthy, S. Drewlo, J. Kingdom, E. J. Johns, S. K. Walsh, and L. C. Kenny, “Peroxisome proliferator-activated receptor-γ as a potential therapeutic target in the treatment of preeclampsia,” Hypertension, vol. 58, no. 2, pp. 280–286, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. M. E. Street, P. Seghini, S. Feini et al., “Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls,” European Journal of Endocrinology, vol. 155, no. 4, pp. 567–574, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Desai, Guang Han, M. Ferelli, N. Kallichanda, and R. H. Lane, “Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring,” Reproductive Sciences, vol. 15, no. 8, pp. 785–796, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. W. T. Schaiff, I. Bildirici, M. Cheong, P. L. Chern, D. M. Nelson, and Y. Sadovsky, “Peroxisome proliferator-activated receptor-γ and retinoid X receptor signaling regulate fatty acid uptake by primary human placental Trophoblasts,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 7, pp. 4267–4275, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. F. P. McCarthy, S. Drewlo, F. A. English et al., “Evidence implicating peroxisome proliferator-activated receptor-γ in the pathogenesis of preeclampsia,” Hypertension, vol. 58, no. 5, pp. 882–887, 2011. View at Google Scholar
  42. M. Lappas, M. Permezel, H. M. Georgiou, and G. E. Rice, “Regulation of proinflammatory cytokines in human gestational tissues by peroxisome proliferator-activated receptor-γ: effect of 15-deoxy-δ12,14-PGJ2 and troglitazone,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 10, pp. 4667–4672, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Vats, L. Mukundan, J. I. Odegaard et al., “Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation,” Cell Metabolism, vol. 4, no. 1, pp. 13–24, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. J. I. Odegaard, R. R. Ricardo-Gonzalez, M. H. Goforth et al., “Macrophage-specific PPARγ controls alternative activation and improves insulin resistance,” Nature, vol. 447, no. 7148, pp. 1116–1120, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Nagamatsu and D. J. Schust, “The contribution of macrophages to normal and pathological pregnancies,” American Journal of Reproductive Immunology, vol. 63, no. 6, pp. 460–471, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Porcheray, S. Viaud, A. C. Rimaniol et al., “Macrophage activation switching: an asset for the resolution of inflammation,” Clinical and Experimental Immunology, vol. 142, no. 3, pp. 481–489, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. F. O. Martinez, L. Helming, and S. Gordon, “Alternative activation of macrophages: an immunologic functional perspective,” Annual Review of Immunology, vol. 27, pp. 451–483, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Ricote, J. S. Welch, and C. K. Glass, “Regulation of macrophage gene expression by the peroxisome proliferator-activated receptor-γ,” Hormone Research, vol. 54, no. 5-6, pp. 275–280, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Chawla, “Control of macrophage activation and function by PPARs,” Circulation Research, vol. 106, no. 10, pp. 1559–1569, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. M. A. Bouhlel, B. Derudas, E. Rigamonti et al., “PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties,” Cell Metabolism, vol. 6, no. 2, pp. 137–143, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. G. Chinetti, J. C. Fruchart, and B. Staels, “Peroxisome proliferator-activated receptors: new targets for the pharmacological modulation of macrophage gene expression and function,” Current Opinion in Lipidology, vol. 14, no. 5, pp. 459–468, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Sica and A. Mantovani, “Macrophage plasticity and polarization: in vivo veritas,” The Journal of Clinical Investigation, vol. 122, no. 3, pp. 787–795, 2012. View at Google Scholar
  53. L. Mukundan, J. I. Odegaard, C. R. Morel et al., “PPAR-Δ senses and orchestrates clearance of apoptotic cells to promote tolerance,” Nature Medicine, vol. 15, no. 11, pp. 1266–1272, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Dong, J. He, Z. Wang, X. Xie, and H. Wang, “Placental imbalance of Th1- and Th2-type cytokines in preeclampsia,” Acta Obstetricia et Gynecologica Scandinavica, vol. 84, no. 8, pp. 788–793, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Banerjee, A. Smallwood, J. Moorhead et al., “Placental expression of interferon-γ (IFN-γ) and its receptor IFN-γR2 fail to switch from early hypoxic to late normotensive development in preeclampsia,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 2, pp. 944–952, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Szekeres-Bartho, M. Halasz, and T. Palkovics, “Progesterone in pregnancy; receptor-ligand interaction and signaling pathways,” Journal of Reproductive Immunology, vol. 83, no. 1-2, pp. 60–64, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. S. E. Dunn, R. Bhat, D. S. Straus et al., “Peroxisome proliferator-activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity,” Journal of Experimental Medicine, vol. 207, no. 8, pp. 1599–1608, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. T. M. Lindström and P. R. Bennett, “15-Deoxy-Δ12, 14-prostaglandin J2 inhibits interleukin-1β-induced nuclear factor-κB in human amnion and myometrial cells: mechanisms and implications,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 6, pp. 3534–3543, 2005. View at Google Scholar
  59. D. Chiron, I. Bekeredjian-Ding, C. Pellat-Deceunynck, R. Bataille, and G. Jego, “Toll-like receptors: lessons to learn from normal and malignant human B cells,” Blood, vol. 112, no. 6, pp. 2205–2213, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Carbone, A. Gallego, N. Lanio et al., “Quantitative abnormalities of peripheral blood distinct T, B, and natural killer cell subsets and clinical findings in obstetric antiphospholipid syndrome,” Journal of Rheumatology, vol. 36, no. 6, pp. 1217–1225, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. C. C. Zhou, S. Ahmad, T. Mi et al., “Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling,” Hypertension, vol. 51, no. 4, pp. 1010–1019, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. B. Lamarca, K. Wallace, F. Herse et al., “Hypertension in response to placental ischemia during pregnancy: role of B lymphocytes,” Hypertension, vol. 57, no. 4, pp. 865–871, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. D. M. Ray, F. Akbiyik, S. H. Bernstein, and R. P. Phipps, “CD40 engagement prevents peroxisome proliferator-activated receptor γ agonist-induced apoptosis of B lymphocytes and B lymphoma cells by an NF-κB-dependent mechanism,” The Journal of Immunology, vol. 174, no. 7, pp. 4060–4069, 2005. View at Google Scholar · View at Scopus
  64. T. M. Garcia-Bates, C. J. Baglole, M. P. Bernard, T. I. Murant, P. J. Simpson-Haidaris, and R. P. Phipps, “Peroxisome proliferator-activated receptor γ ligands enhance human B cell antibody production and differentiation,” The Journal of Immunology, vol. 183, no. 11, pp. 6903–6912, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. J. Zhang, Z. Chen, G. N. Smith, and B. A. Croy, “Natural killer cell-triggered vascular transformation: maternal care before birth?” Cellular and Molecular Immunology, vol. 8, no. 1, pp. 1–11, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. P. Vacca, C. Cantoni, M. Vitale et al., “Crosstalk between decidual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 26, pp. 11918–11923, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Lin, Y. Zhong, W. Shen et al., “TSLP-induced placental DC activation and IL-10+ NK cell expansion: comparative study based on BALB/c × C57BL/6 and NOD/SCID × C57BL/6 pregnant models,” Clinical Immunology, vol. 126, no. 1, pp. 104–117, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. I. T. González, G. Barrientos, N. Freitag et al., “Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression,” PLoS One, vol. 7, no. 10, Article ID e46755, 2012. View at Google Scholar
  69. A. R. French and W. M. Yokoyama, “Natural killer cells and viral infections,” Current Opinion in Immunology, vol. 15, no. 1, pp. 45–51, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. X. Zhang, M. C. Rodriguez-Galán, J. J. Subleski et al., “Peroxisome proliferator-activated receptor-γ and its ligands attenuate biologic functions of human natural killer cells,” Blood, vol. 104, no. 10, pp. 3276–3284, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Gosset, A.-S. Charbonnier, P. Delerive et al., “Peroxisome proliferator-activated receptor γ activators affect the maturation of human monocyte-derived dendritic cells,” European Journal of Immunology, vol. 31, no. 10, pp. 2857–2865, 2001. View at Google Scholar
  72. A. Nencioni, F. Grünebach, A. Zobywlaski, C. Denzlinger, W. Brugger, and P. Brossart, “Dendritic cell immunogenicity is regulated by peroxisome proliferator-activated receptor γ,” The Journal of Immunology, vol. 169, no. 3, pp. 1228–1235, 2002. View at Google Scholar · View at Scopus
  73. G. Desoye and S. Hauguel-De Mouzon, “The human placenta in gestational diabetes mellitus: the insulin and cytokine network,” Diabetes Care, vol. 30, no. 2, pp. S120–S126, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. B. Huppertz, “Placental origins of preeclampsia: challenging the current hypothesis,” Hypertension, vol. 51, no. 4, pp. 970–975, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. M. F. Chammas, T. M. Nguyen, M. A. Li, B. S. Nuwayhid, and L. C. Castro, “Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?” American Journal of Obstetrics and Gynecology, vol. 183, no. 4, pp. 853–858, 2000. View at Publisher · View at Google Scholar · View at Scopus
  76. J. J. Walker, “Pre-eclampsia,” The Lancet, vol. 356, no. 9237, pp. 1260–1265, 2000. View at Google Scholar · View at Scopus
  77. L. A. Barbour, C. E. McCurdy, T. L. Hernandez, J. P. Kirwan, P. M. Catalano, and J. E. Friedman, “Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes,” Diabetes Care, vol. 30, supplement 2, pp. S112–S119, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Hawfield and B. I. Freedman, “Pre-eclampsia: the pivotal role of the placenta in its pathophysiology and markers for early detection,” Therapeutic Advances in Cardiovascular Disease, vol. 3, no. 1, pp. 65–73, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. J. S. Gilbert, M. J. Ryan, B. B. Lamarca, M. Sedeek, S. R. Murphy, and J. P. Granger, “Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction,” American Journal of Physiology, vol. 294, no. 2, pp. H541–H550, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Jawerbaum, E. Capobianco, C. Pustovrh et al., “Influence of peroxisome proliferator-activated receptor γ activation by its endogenous ligand 15-deoxy Δ 1214 prostaglandin J2 on nitric oxide production in term placental tissues from diabetic women,” Molecular Human Reproduction, vol. 10, no. 9, pp. 671–676, 2004. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Lappas, M. Permezel, and G. E. Rice, “Release of proinflammatory cytokines and 8-isoprostane from placenta, adipose tissue, and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 11, pp. 5627–5633, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. L. Sykes, D. A. MacIntyre, X. J. Yap, S. Ponnampalam, T. G. Teoh, and P. R. Bennett, “Changes in the Th1:Th2 cytokine bias in pregnancy and the effects of the anti-inflammatory cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2,” Mediators of Inflammation, vol. 2012, Article ID 416739, 12 pages, 2012. View at Publisher · View at Google Scholar
  83. W. T. Schaiff, Y. Barak, and Y. Sadovsky, “The pleiotropic function of PPARγ in the placenta,” Molecular and Cellular Endocrinology, vol. 249, no. 1-2, pp. 10–15, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. H. Martin, “Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components,” Mutation Research, vol. 669, no. 1-2, pp. 1–7, 2009. View at Publisher · View at Google Scholar · View at Scopus