한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제19권4호
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  • Pages.243-252
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  • 2015
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  • 2465-9525(pISSN)
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  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
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Th 17 Cells and Nesfatin-1 are associated with Spontaneous Abortion in the CBA/j×DBA/2 Mouse Model

  • Chung, Yiwa (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University) ;
  • Kim, Heejeong (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University) ;
  • Im, Eunji (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University) ;
  • Kim, Philjae (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University) ;
  • Yang, Hyunwon (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
  • 투고 : 2015.11.29
  • 심사 : 2015.12.15
  • 발행 : 2015.12.31
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초록

The pregnancy and abortion process involves a complex mechanism with various immune cells present in the implantation sites and several hormones associated with pregnancy, such as leptin, ghrelin and nesfatin-1. However, the mechanism underlying spontaneous abortion by maternal T helper 17 (Th17) present in the implantation sites and nesfatin-1, which is of anorexigenic hormones, is not fully understood so far. Therefore, the purpose of this study was to examine the possible roles of Th17 cells present in the implantation sites and nesfatin-1 expressed in the uterus on spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Th17 transcription factor, ROR-${\gamma}t$ mRNA expression was significantly increased in the abortion sites compared with the implantation sites of abortion model mice on day 14.5 and 19.5 of pregnancy. In addition, the expression levels of IL-17A mRNA were significantly higher in abortion sites than in implantation sites on day 14.5 and 19.5. Moreover, the nesfatin-1/NUCB2 protein and mRNA levels were increased in abortion sites compared with levels in implantation sites of both normal pregnant and abortion model mice on day 14.5 of pregnancy. Interestingly, nesfatin-1/NUCB2 serum levels were not changed throughout the whole pregnancy in abortion model mice, but its serum level was dramatically increased on day 14.5, and then rapidly decreased on day 19.5 in normal pregnant mice. In this study, we showed for the first time the expression of nesfatin-1/NUCB2 mRNA and protein in implantation sites during pregnancy. The present results suggest that Th17 cells in the uterus may play an important role in the period of implantation and for maintenance of pregnancy. Furthermore, the present results suggest that Th17 cells in implantation sites may be a key regulator for maintenance of pregnancy and provides evidence that activation of these cells may be regulated by nesfatin-1/NUCB2. Further study is needed to elucidate the role of nesfatin-1 expressed in the uterus during pregnancy.

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참고문헌

  1. Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5:266-271. https://doi.org/10.1038/ni1037
  2. Crome SQ, Wang AY, Levings MK (2010) Translational mini-review series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 159:109-119. https://doi.org/10.1111/j.1365-2249.2009.04037.x
  3. Ford HB, Schust DJ (2009) Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2:76-83.
  4. Garces MF, Poveda NE, Sanchez E, Sanchez AY, Bravo SB, Vazquez MJ, Dieguez C, Nogueiras R, Caminos JE (2014) Regulation of NucB2/Nesfatin-1 throughout rat pregnancy. Physiol Behav 133:216-222. https://doi.org/10.1016/j.physbeh.2014.05.042
  5. Garcia-Galiano D, Navarro VM, Gaytan F, Tena-Sempere M (2010) Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation. J Mol Endocrinol 45:281-290. https://doi.org/10.1677/JME-10-0059
  6. Garcia-Galiano D, Pineda R, Ilhan T, Castellano JM, Ruiz-Pino F, Sanchez-Garrido MA, Vazquez MJ, Sangiao-Alvarellos S, Romero-Ruiz A, Pinilla L, Dieguez C, Gaytan F, Tena-Sempere M (2012) Cellular distribution, regulated expression, and functional role of the anorexigenic peptide, NUCB2/nesfatin-1, in the testis. Endocrinology 153:1959-1971. https://doi.org/10.1210/en.2011-2032
  7. Goebel M, Stengel A, Wang L, Lambrecht NW, Tache Y (2009) Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett 452:241-246. https://doi.org/10.1016/j.neulet.2009.01.064
  8. Gonzalez R, Shepperd E, Thiruppugazh V, Lohan S, Grey C, Chang JP, Unniappan S (2012) Nesfatin-1 regulates the hypothalamo-pituitary-ovarian axis of fish. Biol Reprod 87:1-11. https://doi.org/10.1095/biolreprod.112.101691
  9. Gonzalez RR, Simon C, Caballero-Campo P, Norman R, Chardonnens D, Devoto L, Bischof P (2000) Leptin and reproduction. Hum Reprod Update 6:290-300. https://doi.org/10.1093/humupd/6.3.290
  10. Gualillo O, Caminos JE, Nogueiras R, Seoane LM, Arvat E, Ghigo E, Casanueva FF, Dieguez C (2002) Effect of food restriction on ghrelin in normal-cycling female rats and in pregnancy. Obes Res 10:682-687. https://doi.org/10.1038/oby.2002.92
  11. Kaitu'u-Lino TJ, Morison NB, Salamonsen LA (2007) Neutrophil depletion retards endometrial repair in a mouse model. Cell Tissue Res 328:197-206. https://doi.org/10.1007/s00441-006-0358-2
  12. Kim J, Kim H, Kim S, Yang H, Cho H, Hwang S, Moon C, Yang H (2011) Expression of nesfatin-1/NUCB2 and its binding site in mouse testis and epididymis. Dev Reprod 15:249-256.
  13. Kim J, Yang H (2012) Nesfatin-1 as a new potent regulator in reproductive system. Dev Reprod 16: 253-264. https://doi.org/10.12717/DR.2012.16.4.253
  14. Kim J, Youn M, Bang S, Sim J, Kang H, Yang H (2010) Expression of nesfatin-1/NUCB2 and its binding site in mouse ovary. Dev Reprod 14:287-295.
  15. Lin H, Mossmann TR, Guilbert L, Tuntipopipat S, Wegmann TG (1993) Synthesis of T helper 2-type cytokines at the feto-maternal interface. J Immunol 151:4562-4573.
  16. Luque EM, Torres PJ, de Loredo N, Vincenti LM, Stutz G, Santillan ME, Ruiz RD, de Cuneo MF, Martini AC (2014) Role of ghrelin in fertilization, early embryo development, and implantation periods. Reproduction 148:159-167. https://doi.org/10.1530/REP-14-0129
  17. Makriagiannis A, Zoumakis E, Kalantaridou C, Coutifaris C, MargiorisAN, Coukos G, Rice KC, Gravansi A, Chrousos GP (2001) Corticotropinreleasing hormone promotes blastocytes implantation and early maternal tolerance. Nat Immunol 18:367-391.
  18. Mimee A, Smith PM, Ferguson AV (2012) Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function. Am J Physiol Regul Integr Comp Physiol 302:1297-1304. https://doi.org/10.1152/ajpregu.00266.2011
  19. Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S (2010a) Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol 64:4-11.
  20. Nakashima A, Ito M, Yoneda S, Shiozaki A, Hidaka T, Saito S (2010b) Circulating and decidual Th17 cell levels in healthy pregnancy. Am J Reprod Immunol 64:104-109.
  21. Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, Eguchi H, Yamamoto M, Imaki T, Hashimoto K, Tsuchiya T, Monden T, Horiguchi K, Yamada M, Mori M (2006) Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 443:709-712. https://doi.org/10.1038/nature05162
  22. Piccinni MP, Beloni L, Livi C, Maggi E, Scarselli G, Romagnani S (1998) Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat Med 4:1020-1024. https://doi.org/10.1038/2006
  23. Raghupathy R (1997) Th1-type immunity is incompatible with successful pregnancy. Immunol Today 18:478-482. https://doi.org/10.1016/S0167-5699(97)01127-4
  24. Ramanjaneya M, Chen J, Brown JE, Tripathi G, Hallschmid M, Patel S, Kern W, Hillhouse EW, Lehnert H, Tan BK, Randeva HS (2010) Identification of nesfatin-1 in human and murine adipose tissue: a novel depot specific adipokine with increased levels in obesity. Endocrinology 151:3169-3180. https://doi.org/10.1210/en.2009-1358
  25. Robertson SA (2000) Control of the immunological environment of the uterus. Rev Reprod 5:164-174. https://doi.org/10.1530/ror.0.0050164
  26. Saifi B, Rezaee SA, Tajik N, Ahmadpour ME, Ashrafi M, Vakili R, SoleimaniAsl S, Aflatoonian R, Mehdizadeh M (2014) Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. Reprod Biomed Online 29:481-489. https://doi.org/10.1016/j.rbmo.2014.06.008
  27. Shimizu H, Ohsaki A, Oh-I S, Okada S, Mori M (2009) A new anorexigenic protein, nesfatin-1. Peptides 30:995-998. https://doi.org/10.1016/j.peptides.2009.01.002
  28. Sonoda Y, Mukaida N, Wang JB, Shimada-Hiratsuka M, Naito M, Kasahara T, Harada A, Inoue M, Matsushima K (1998) Physiologic regulation of postovulatory neutrophil migration into vagina in mice by a C-X-C chemokine(s). J Immunol 160:6159-6165.
  29. Steffl M, Telgen L, Schweiger M, Amselgruber WM (2010) Estrous cycle-dependent activity of neutrophils in the porcine endometrium: possible involvement of heat shock protein 27 and lactoferrin. Anim Reprod Sci 121:159-166.
  30. Stengel A, Goebel M, Tache Y (2010) Nesfatin-1: a novel inhibitory regulator of food intake and body weight. Obes Rev 12:261-271.
  31. Stengel A, Goebel M, Wang L, Rivier J, Kobelt P, Monnikes H, Lambrecht NW, Tache Y (2009a) Central nesfatin-1 reduces darkphase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor 2 receptor. Endocrinology 150:4911-4919. https://doi.org/10.1210/en.2009-0578
  32. Stengel A, Goebel M, Wang L, Tache Y (2009b) Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight. Peptides 31:357-369.
  33. Tafuri A, Alferink J, Moller P, Hammerling G, Arnold B (1995) T cell awareness of paternal alloantigens during pregnancy. Science 270:630-633. https://doi.org/10.1126/science.270.5236.630
  34. Trowsdale J, Betz AG (2006) Mother’s little helpers: mechanisms of maternal-fetal tolerance. Nat Immunol 7:241-246.
  35. von Boehmer H (2005) Mechanisms of suppression by suppressor T cells. Nat Immunol 6:338-344. https://doi.org/10.1038/ni1180
  36. Waldmann H, Graca L, Cobbold S, Adams E, Tone M, Tone Y (2004) Regulatory T cells and organ transplantation. Semin Immunol 16:119-126. https://doi.org/10.1016/j.smim.2003.12.007
  37. Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD (2010b) The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Hum Reprod 25:2591-2596. https://doi.org/10.1093/humrep/deq198
  38. Wang WJ, Hao CF, Yi-Lin, Yin GJ, Bao SH, Qiu LH, Lin QD (2010a) Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 84:164-170. https://doi.org/10.1016/j.jri.2009.12.003
  39. Wang WJ, Liu FJ, Xin-Liu, Hao CF, Bao HC, Qu QL, Liu XM (2014) Adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA/J x BALB/c mouse model. Hum Reprod 29:946-952. https://doi.org/10.1093/humrep/deu014
  40. Xia ZF, Fritze DM, Li JY, Chai B, Zhang C, Zhang W, Mulholland MW (2012) Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats. Am J Physiol Gastrointest Liver Physiol 303:570-577. https://doi.org/10.1152/ajpgi.00178.2012
  41. Xu WM, Xiao ZN, Wang XB, Huang Y (2015) IL-17 induces fetal loss in a CBA/J${\times}$BALB/c mouse model, and an anti-IL-17 antibody prevents fetal loss in a CBA/J ${\times}$ DBA/2 Mouse Model. Am J Reprod Immunol [Epub ahead of print]
  42. Yoon SJ, Cha KY, Lee KA (2005) Leptin receptors are down-regulated in uterine implantation sites compared to interimplantation sites. Mol Cell Endocrinol 232:27-35. https://doi.org/10.1016/j.mce.2005.01.002
  43. Yosten GL, Redlinger L, Samson WK (2012) Evidence for a role of endogenous nesfatin-1 in the control of water drinking. J Neuroendocrinol 24:1078-1084. https://doi.org/10.1111/j.1365-2826.2012.02304.x
  44. Zenclussen AC, Schumacher A, Laura M, Zenclussen, Wafula P, Volk HD (2007) Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus. Expert Rev Mol Med 9:1-14.