Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Serum Leptin Levels in Women with Immunological Recurrent Abortion

Authors
Saeed Zarei 1
Haleh Soltanghoraee 2
Afsaneh Mohammadzadeh 2
Soheila Arefi 2
Amir Hassan Zarnani 3
Farah Idali 2
Banafsheh Tavangar 1
Elham Savadi-Shiraz 2
Narges Moshref Behzad 2
Mahmood Jeddi-Tehrani 1
1 Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
2 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
3 Nanobiotechnology Research Center, Avicenna Research Institute (ACECR), Tehran, Iran; Immunology Research Center, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Introduction: Recurrent abortion (RA) may be a consequence of aberrant expression of immunological factors during pregnancy. Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that autoantibodies contribute to reproductive failure. Production of such antibodies is under the control of cytokines; and leptin, besides its role in reproductive success, has a profound effect on directing the cytokine profile toward Th1 (cellular) pattern. Therefore, the present study was performed to assess serum leptin levels in women with immunological recurrent abortion.Materials and Methods: In this prospective study, 250 women who attended Avicenna Infertility Clinic with RA were screened for known causes of abortion from July to December 2008 in Tehran, Iran. Eighty-one patients with normal karyotypes and hormonal profile with normal ovaries and uterus and no signs of infection were categorized as patients with immunological (IRA, n = 39) or unexplained (URA, n = 42) recurrent abortion based on presence or absence of autoantibodies. After blood sampling, levels of anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA), lupus anti-coagulant antibody (LACAb), anti-phospholipid antibody (APA), anti-cardiolipin antibody (ACA), anti-thyroglobulin antibody (TgAb), anti-thyroperoxidase antibody (TPOAb) and anti-thrombin III antibody (ATIIIAb) were measured by enzyme-linked immunosorbent assay (ELISA) or chemiluminescent enzyme immunoassay (CLEIA).Results: In IRA group, 9 (23.1%), 24 (61.5%), 25(64.1%) and 1 (2.6%) women were above the normal cut-off point for ANA, TgAbs, TPOAbs and AT-III Abs, respectively. IRA patients had normal values of LACAbs, APA and ACA. With normal level of fasting blood sugar (FBS), IRA and URA groups had similar serum leptin levels (23.7  13.2 ng/ml vs. 22.7  12.5 ng/ml, respectively). Serum leptin concentrations showed a positive correlation with weight and BMI in both groups.Conclusion: This study suggests that serum leptin levels are higher in IRA and URA patients than normal women. The findings of this study suggest the need for a more comprehensive study and comparison of leptin levels in IRA and URA patients to women with no history of miscarriages.
Keywords
autoantibody
ELISA
Immunological
leptin
Pregnancy
Recurrent abortion
Spontaneous abortion
  1. Cramer DW, Wise LA. The epidemiology of recur-rent pregnancy loss. Semin Reprod Med. 2000;18 (4):331-9.
  2. Gleicher N, Friberg J. IgM gammopathy and the lupus anticoagulant syndrome in habitual aborters. JAMA. 1985;253(22):3278-81.
  3. Xu L, Chang V, Murphy A, Rock JA, Damewood M, Schlaff W, et al. Antinuclear antibodies in sera of patients with recurrent pregnancy wastage. Am J Obstet Gynecol. 1990;163(5 Pt 1):1493-7.
  4. Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detec-tion of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990;264(11):1422-5.
  5. Stricker RB, Winger EE. Update on treatment of immunologic abortion with low-dose intravenous immunoglobulin. Am J Reprod Immunol. 2005;54 (6):390-6.
  6. He J, Wang H, Zhao JX, Li ZG. [Establishment of Sjogren's syndrome models by immunization with alpha-Fodrin: experiment with mice]. Zhonghua Yi Xue Za Zhi. 2008;88(33):2360-3. Chinese.
  7. Mosaad YM, Metwally SS, Auf FA, AbdEL-Samee ER, el-Deek B, Limon NI, et al. Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases: relation with disease activity and auto-antibodies production. Egypt J Immunol. 2003;10 (2):19-26.
  8. Spadaro M, Amendolea MA, Mazzucconi MG, Fantozzi R, Di Lello R, Zangari P, et al. Autoimmunity in multiple sclerosis: study of a wide spectrum of autoantibodies. Mult Scler. 1999;5(2): 121-5.
  9. Enghard P, Langnickel D, Riemekasten G. T cell cytokine imbalance towards production of IFN-gamma and IL-10 in NZB/W F1 lupus-prone mice is associated with autoantibody levels and nephritis. Scand J Rheumatol. 2006;35(3):209-16.
  10. Graphou O, Chioti A, Pantazi A, Tsukoura C, Kontopoulou V, Guorgiadou E, et al. Effect of intravenous immunoglobulin treatment on the Th1/Th2 balance in women with recurrent spontan-eous abortions. Am J Reprod Immunol. 2003;49 (1):21-9.
  11. Zhang JA, Zhang J, Xu L, Mar H, Wu XY. [Measurement of IL-12 and IL-18 in sera of patients with autoimmune thyroid disease]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2006;22(5):630-2. Chinese.
  12. Gérard AC, Boucquey M, van den Hove MF, Colin IM. Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1alpha/IFN-gamma, an effect partially mediated by nitric oxide. Am J Physiol Endocrinol Metab. 2006;291 (2):E242-53.
  13. Förster G, Otto E, Hansen C, Ochs K, Kahaly G. Analysis of orbital T cells in thyroid-associated ophthalmopathy. Clin Exp Immunol. 1998;112(3): 427-34.
  14. Clark DA, Ding JW, Chaouat G, Coulam CB, August C, Levy GA. The emerging role of immunoregulation of fibrinogen-related procoagu-lant Fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans. Am J Reprod Immunol. 1999;42(1):37-43
  15. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature.1994;372(6505):425-32.
  16. Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996;12(3):318-20.
  17. Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, et al. Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes. 1995;44(7):855-8.
  18. Schubring C, Kiess W, Englaro P, Rascher W, Dötsch J, Hanitsch S, et al. 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(5):1480-3.
  19. Malik NM, Carter ND, Wilson CA, Scaramuzzi RJ, Stock MJ, Murray JF. Leptin expression in the fetus and placenta during mouse pregnancy. Placenta. 2005;26(1):47-52.
  20. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394(6696):897-901.
  21. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol. 2005;174(11):6820-8.
  22. Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, et al. Leptin regulates proinflam-matory immune responses. FASEB J. 1998;12(1): 57-65.
  23. Lage M, Garcia-Mayor RV, Tomé MA, Cordido F, Valle-Inclan F, Considine RV, et al. Serum leptin levels in women throughout pregnancy and the postpartum period and in women suffering spontaneous abortion. Clin Endocrinol (Oxf). 1999;50(2):211-6.
  24. Choi HK, Choi BC, Lee SH, Kim JW, Cha KY, Baek KH. Expression of angiogenesis- and apoptosis-related genes in chorionic villi derived from recurrent pregnancy loss patients. Mol Reprod Dev. 2003;66(1):24-31.
  25. Honkanen H, Ranta S, Ylikorkala O, Heikinheimo O. Effect of antiprogesterone mifepristone followed by misoprostol on circulating leptin in early pregnancy. Acta Obstet Gynecol Scand. 2005;84 (2):134-9.
  26. Laird SM, Quinton ND, Anstie B, Li TC, Blakemore AI. Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome. Hum Reprod. 2001;16 (9):2008-13.
  27. Makrydimas G, Vandecruys H, Sotiriadis A, Laka-sing L, Spencer K, Nicolaides KH. Coelomic fluid leptin concentration in normal first-trimester pregnancies and missed miscarriages. Fetal Diagn Ther. 2005;20(5):406-9.
  28. Tommaselli GA, Di Spiezio Sardo A, Di Carlo C, Bifulco G, Cerrota G, Cirillo D, et al. Do serum leptin levels have a role in the prediction of pregnancy outcome in case of threatened miscar-riage? Clin Endocrinol (Oxf). 2006;65(6):772-5.
  29. Morton GJ. Hypothalamic leptin regulation of energy homeostasis and glucose metabolism. J Physiol. 2007;583(Pt 2):437-43.
  30. Nyström F, Ekman B, Osterlund M, Lindström T, Ohman KP, Arnqvist HJ. Serum leptin concen-trations in a normal population and in GH deficiency: negative correlation with testosterone in men and effects of GH treatment. Clin Endocrinol (Oxf). 1997;47(2):191-8.
  31. Piccinni MP, Beloni L, Livi C, Maggi E, Scarselli G, Romagnani S. Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat Med. 1998;4(9):1020-4.
  32. Barkan D, Hurgin V, Dekel N, Amsterdam A, Rubinstein M. Leptin induces ovulation in GnRH-deficient mice. FASEB J. 2005;19(1):133-5.
  33. Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, et al. Leptin is a metabolic signal to the reproductive system. Endocrinology. 1996;137(7):3144-7.
  34. Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology. 1997;138(3):1190-3.
Journal of Reproduction & Infertility
Volume 11, Issue 1
Spring 2010
Pages 47-52