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Semin Reprod Med 2002; 20(2): 131-138
DOI: 10.1055/s-2002-32504
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Leptin and Preeclampsia

Lucilla Poston
  • Professor of Maternal and Fetal Health, Maternal and Fetal Research Unit, Guy's Kings and St. Thomas' School of Medicine, King's College, London, United Kingdom
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Publication History

Publication Date:
27 June 2002 (online)

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ABSTRACT

Preeclampsia, a common complications of pregnancy, is associated with an increase in the concentration of leptin in the maternal blood, which precedes the clinical onset of the disease. This review addresses the potential sources of leptin and considers the possible consequences, although at present these are entirely conjectural. The placenta is likely to contribute to the rise in leptin, and placental hypoxia and inflammatory mediators may be important stimuli. The possible protective and damaging sequelae of an increase in the maternal leptin concentrations may range from beneficial stimulation of fetal growth to an increase in blood pressure through stimulation of sympathetic activity. Further research is needed to determine if the rise in leptin plays a role in preeclampsia or whether it is a secondary and unrelated bystander.

KEYWORDS

Preeclampsia - pregnancy - leptin

REFERENCES

  • 1 De Swiet M. Maternal mortality: confidential enquiries into maternal deaths in the United Kingdom.  Am J Obstet Gynecol . 2000;  182 760-766
    CrossrefPubMedGoogle Scholar
  • 2 Why mothers die 1997-1999. The Confidential Enquiries into Maternal Deaths. London: RCOG Press 2001
    Google Scholar
  • 3 Dekker G A, Sibai B M. Etiology and pathogenesis of preeclampsia: current concepts.  Am J Obstet Gynecol . 1999;  181 1037
    PubMedGoogle Scholar
  • 4 Saftlas A F, Olson D R, Franks A L, Atrash H K, Pokras R. Epidemiology of preeclampsia and eclampsia in the United States 1979-1986.  Am J Obstet Gynaecol . 1990;  163 460-465
    PubMedGoogle Scholar
  • 5 Levine R J, Hauth J C, Curet L B. Trial of calcium to prevent preeclampsia.  N Engl J Med . 1997;  337 69-76
    CrossrefPubMedGoogle Scholar
  • 6 Roberts J M, Redman C W. Pre-eclampsia: more than pregnancy-induced hypertension.  Lancet . 1993;  341 1447-1451
    CrossrefPubMedGoogle Scholar
  • 7 Higgins J R, de Swiet M. Blood pressure measurement and classification in pregnancy.  Lancet . 2001;  357 131-135
    CrossrefPubMedGoogle Scholar
  • 8 Roberts J M, Cooper D W. Pathogenesis and genetics of pre-eclampsia.  Lancet . 2001;  357 53-56
    CrossrefPubMedGoogle Scholar
  • 9 Roberts J M, Hubel C A. Is oxidative stress the link in the two-stage model of pre-eclampsia?.  Lancet . 1999;  354 788-789
    CrossrefPubMedGoogle Scholar
  • 10 Hubel C A, Roberts J M. Lipid metabolism and oxidative stress. In: Lindheimer MD, Roberts JM, Cunningham G, eds. Chesley's Hypertensive Disorders in Pregnancy Stamford, CT: Appleton & Lang 1999: 453-486
    Google Scholar
  • 11 Poston L. Oxidative stress, pre-eclampsia, and antioxidants.  Reprod Vasc Med . 2001;  1 107-113
    PubMedGoogle Scholar
  • 12 Considine R C, Sinha M K, Heiman M L. Serum immunoreactive-leptin concentration in normal weight and obese human.  N Eng J Med . 1996;  334 292-295
    CrossrefPubMedGoogle Scholar
  • 13 Segal K R, Landt M, Klein S. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men.  Diabetes . 1996;  45 988-991
    PubMedGoogle Scholar
  • 14 Schubring C, Englaro P, Siebler T. Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels.  Horm Res . 1998;  50 276-283
    CrossrefPubMedGoogle Scholar
  • 15 Geary M, Pringle P J, Persaud M. Leptin concentrations in maternal serum and cord blood: relationship to maternal anthropometry and fetal growth.  Br J Obstet Gynaecol . 1999;  106 1054-1060
    PubMedGoogle Scholar
  • 16 McCarthy J F, Misra D N, Roberts J M. Maternal plasma leptin is increased in preeclampsia and positively correlates with fetal cord concentration.  Am J Obstet Gynecol . 1999;  180 731-736
    CrossrefPubMedGoogle Scholar
  • 17 Masuzaki H, Ogawa Y, Sagawa N. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans.  Nat Med . 1997;  3 1029-1033
    CrossrefPubMedGoogle Scholar
  • 18 Laird S M, Quinton N D, Anstie B, Li T C, Blakemore A I. Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome.  Hum Reprod . 2001;  16 2009-2013
    PubMedGoogle Scholar
  • 19 Green E D, Maffei M, Braden V V. The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenic, and genetic maps of chromosome 7.  Genome Res . 1995;  5 5-12
    PubMedGoogle Scholar
  • 20 Lea R G, Howe D, Hannah L T, Bonneau O, Hunter L, Hoggard N. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies.  Mol Hum Reprod . 2000;  6 763-769
    CrossrefPubMedGoogle Scholar
  • 21 Bi S, Gavrilova O, Gong D W. Identification of a placental enhancer for the human leptin gene.  J Biol Chem . 1997;  272 30583-30588
    CrossrefPubMedGoogle Scholar
  • 22 Schubring C, Keiss W, Englaro P. Levels of leptin in maternal serum, amniotic fluid and arterial and venous cord blood: relation to neonatal and placental weight.  J Clin Endocrinol Metab . 1997;  82 1480-1483
    CrossrefPubMedGoogle Scholar
  • 23 Eskenazi B, Fenster L, Sydney S. A multivariate analysis of risk factors for pre-eclampsia.  JAMA . 1991;  266 237-241
    CrossrefPubMedGoogle Scholar
  • 24 Solomon C G, Seely E W. Hypertension in pregnancy: a manifestation of the insulin resistance syndrome?.  Hypertension . 2001;  37 232-239
    PubMedGoogle Scholar
  • 25 Lorentzen B, Henriksen T. Plasma lipids and vascular dysfunction in pre-eclampsia.  Semin Reprod Endocrinol . 1998;  16 33-39
    PubMedGoogle Scholar
  • 26 Mise H, Sagawa N, Matsumoto T. Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia.  J Clin Endocrinol Metab . 1998;  83 3225-3229
    CrossrefPubMedGoogle Scholar
  • 27 Sattar N, Greer I A, Pirwani I, Gibson J, Wallace M. Leptin levels in pregnancy: marker for fat accumulation and mobilization?.  Acta Obstet Gynecol Scand . 1998;  77 278-283
    CrossrefPubMedGoogle Scholar
  • 28 Williams M A, Havel P J, Schwartz M W. Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women.  Paediatr Perinat Epidemiol . 1999;  13 190-204
    CrossrefPubMedGoogle Scholar
  • 29 Anim-Nyame N, Sooranna S R, Steer P J, Johnson M R. Longitudinal analysis of maternal plasma leptin concentrations during normal pregnancy and pre-eclampsia.  Hum Reprod . 2000;  15 2033-2036
    CrossrefPubMedGoogle Scholar
  • 30 Laivuori H, Kaaja R, Koistinen H. Leptin during and after preeclamptic or normal pregnancy: its relation to serum insulin and insulin sensitivity.  Metabolism . 2000;  49 259-263
    CrossrefPubMedGoogle Scholar
  • 31 Teppa R J, Ness R B, Crombelholme W R, Roberts J M. Free leptin in increased in normal pregnancy and further increased in pre-eclampsia.  Metabolism . 2000;  49 1043-1048
    PubMedGoogle Scholar
  • 32 Vitoratos N, Chrystodoulacos G, Kouskouni E, Salamalekis E, Creatsas G. Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy.  Euro J Obstet Gynecol Reprod Biol . 2001;  96 59-62
    PubMedGoogle Scholar
  • 33 Laml T, Preyer O, Hartmann B W, Ruecklinger E, Soeregi G, Wagenbichler P. Decreased maternal serum leptin in pregnancies complicated by preeclampsia.  J Soc Gynecol Invest . 2001;  8 89-93
    CrossrefPubMedGoogle Scholar
  • 34 Chappell L C, Seed P T, Briley A. A longitudinal study of biochemical variables in women at risk of pre-eclampsia (in press).  Am J Obstet Gynecol. 2002; 
    PubMedGoogle Scholar
  • 35 Kolaczynski J W, Goldstein B J, Considine R V. Dexamethasone, OB gene, and leptin in humans: effect of exogenous hyperinsulinemia.  J Clin Endocrinol Metab . 1997;  82 3895-3897
    CrossrefPubMedGoogle Scholar
  • 36 Linnemann K, Malek A, Schneider H, Fusch C. Physiological and pathological regulation of feto/placento/maternal leptin expression.  Biochem Soc Trans . 2001;  29 86-90
    CrossrefPubMedGoogle Scholar
  • 37 Hartmann B W, Wagenbichler P, Soregi G. Maternal and umbilical-cord serum leptin concentrations in normal, full-term pregnancies [letter].  N Engl J Med . 1997;  337 863
    CrossrefPubMedGoogle Scholar
  • 38 Butte N F, Hopkinson J M, Nicolson M A. Leptin in human reproduction: serum leptin levels in pregnant and lactating women.  J Clin Endocrinol Metab . 1997;  82 585-589
    CrossrefPubMedGoogle Scholar
  • 39 Dötsch J, Nüsken K-D, Knerr I, Kirschbaum M, Repp R, Rascher W. Leptin and neuropeptide Y gene expression in human placenta: ontogeny and evidence for similarities to hypothalamic regulation.  J Clin Endocrinol Metab . 1999;  84 2755-2758
    CrossrefPubMedGoogle Scholar
  • 40 Poston L. Non invasive investigation of uteroplacental insufficiency. In: Kingdom JCP, Jauniaux ERM, O'Brien PMS, eds. The Placenta: Basic Science and Clinical Practice London: RCOG Press 2000: 299-308
    Google Scholar
  • 41 Grosfeld A, Turban S, Andre J. Transcriptional effect of hypoxia on placental leptin.  FEBS Lett . 2001;  502 122-126
    CrossrefPubMedGoogle Scholar
  • 42 Redman C WG, Sacks G P, Sargent I L. Pre-eclampsia, an excessive maternal inflammatory response to pregnancy.  Am J Obstet Gynecol . 1999;  180 499-506
    CrossrefPubMedGoogle Scholar
  • 43 Sacks G P, Studena K, Sargent K, Redman C WG. Normal pregnancy and pre-eclampsia both produce inflammatory changes in peripheral blood leucocytes akin to those of sepsis.  Am J Obstet Gynecol . 1998;  179 80-86
    CrossrefPubMedGoogle Scholar
  • 44 Zhang F, Basinski M B, Beals J M. Crystal structure of the obese protein leptin-E100.  Nature . 1997;  387 206-209
    CrossrefPubMedGoogle Scholar
  • 45 Faggioni R, Feinfold K R, Grunfeld C. Leptin regulation of the immune response and the immunodeficiency of malnutrition.  FASEB J . 2001;  15 2566-2571
    PubMedGoogle Scholar
  • 46 Grunfeld C, Zhao C, Fuller J. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters: a role for leptin in the anorexia of infection.  J Clin Invest . 1996;  97 2152-2157
    CrossrefPubMedGoogle Scholar
  • 47 Garcia M D, Casanueva F F, Dieguez C, Senaris R M. Gestational profile of leptin messenger ribonucleic acid (mRNA) content in the placenta and adipose tissue in the rat, and regulation of the mRNA levels of the leptin receptor subtypes in the hypothalamus during pregnancy and lactation.  Biol Reprod . 2000;  62 698-703
    PubMedGoogle Scholar
  • 48 Sierra-Honigmann M R, Nath A K, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa W C. Biological action of leptin as an angiogenic factor.  Science . 1998;  281 1683-1686
    CrossrefPubMedGoogle Scholar
  • 49 Park H Y, Kwon H M, Lim H J. Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro.  Exp Mol Med . 2001;  33 95-110
    PubMedGoogle Scholar
  • 50 Hoggard N, Haggarty P, Thomas L, Lea R G. Leptin expression in placental and fetal tissues: does leptin have a functional role?.  Biochem Soc Trans . 2001;  29 57-63
    CrossrefPubMedGoogle Scholar
  • 51 Okuya S, Tanabe K, Tanizawa Y, Oka Y. Leptin increases the viability of isolated rat pancreatic islets by suppressing apoptosis.  Endocrinology . 2001;  142 4827-4830
    CrossrefPubMedGoogle Scholar
  • 52 Leung D N, Smith S C, To K F, Sahota D S, Baker P N. Increased placental apoptosis in pregnancies complicated by preeclampsia.  Am J Obstet Gynecol . 2001;  184 1249-1250
    CrossrefPubMedGoogle Scholar
  • 53 Kimura K, Tsuda K, Baba A. Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin.  Biochem Biophys Res Commun . 2000;  273 745-749
    CrossrefPubMedGoogle Scholar
  • 54 Mitchell J L, Morgan D A, Correia M L, Mark A L, Sivitz W I, Haynes W G. Does leptin stimulate nitric oxide to oppose the effects of sympathetic activation?.  Hypertension . 2001;  38 1081-1086
    PubMedGoogle Scholar
  • 55 Takahashi N, Waelput W, Guisez Y. Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor.  J Exp Med . 1999;  189 207-212
    CrossrefPubMedGoogle Scholar
  • 56 Yang S Q, Lin H Z, Lane M D, Clemens M, Diehl A M. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis.  Proc Natl Acad Sci U S A . 1997;  94 2557-2562
    CrossrefPubMedGoogle Scholar
  • 57 Schobel H P, Fischer T, Heuszer K, Geiger H, Schmieder R E. Preeclampsia: a state of sympathetic overactivity.  N Engl J Med . 1996;  335 1480-1485
    CrossrefPubMedGoogle Scholar
  • 58 Hall J E, Hildebrandt D A, Kuo J. Obesity hypertension: role of leptin and sympathetic nervous system.  Am J Hypertens . 2001;  6 103S-115S
    PubMedGoogle Scholar
  • 59 Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes.  Cell Immunol . 2000;  199 15-24
    CrossrefPubMedGoogle Scholar
  • 60 Saito S, Umekage H, Sakamoto Y. Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with preeclampsia.  Am J Reprod Immun . 1999;  41 297-306
    PubMedGoogle Scholar
  • 61 Saito S, Sakai M, Sasaki Y, Tanebe K, Tsuda H, Michimata T. Quantitative analysis of peripheral blood Th0, TH1, TH2 and the TH1: TH2 cell ratio during normal human pregnancy and preeclampsia.  Clin Exp Immunol . 1999;  117 550-555
    CrossrefPubMedGoogle Scholar
  • 62 Kelly B, Stone S, Poston L. Cardiovascular adaptation to pregnancy: the role of altered vascular structure.  Fetal Mat Med Rev . 1999;  11 105-116
    PubMedGoogle Scholar
  • 63 Yamagishi S, Edelstein D, X, Kaneda Y, Guzmán, Brownlee M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A.  J Biol Chem . 2001;  276 25096-25100
    CrossrefPubMedGoogle Scholar
  • 64 Chappell L C, Seed P T, Briley A L. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomized trial.  Lancet . 1999;  354 810-816
    Google Scholar
  • 65 Chappell L C, Stock M J, Seed P T, Poston L. Serum leptin concentrations are abnormal in women at risk of pre-eclampsia and are improved by vitamin C and E supplementation.  J Soc Gynecol Invest. . 2001;  213A
    PubMedGoogle Scholar
  • 66 Erl W, Weber C, Wardemann C, Weber P C. Alpha-tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF-kB mobilization.  Am J Physiol . 1997;  273 H634-640
    PubMedGoogle Scholar
  • 67 Laml T, Hartmann B W, Preyer O, Ruecklinger E, Soeregi G, Wagenbichler P. Serum leptin concentration in cord blood: relationship to birthweight and gender in pregnancies complicated by pre-eclampsia.  Gynecol Endocrinol . 2000;  14 442-447
    PubMedGoogle Scholar
  • 68 Hytinantti T, Koistinen H A, Koivisto V A, Karonen S-L, Rutanen E-M, Andersson S. Increased leptin concentration in preterm infants of pre-eclamptic mothers.  Arch Dis Child Fetal Neonatal Ed . 2000;  83 F13-F16
    PubMedGoogle Scholar
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