Clinical and Experimental Reproductive Medicine

  • 제43권1호
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  • Pages.15-25
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  • 2016
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
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Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy

  • Ahmadabad, Hasan Namdar (Department of Pathobiology and Medical Laboratory Science, School of Medicine, North Khorasan University of Medical Sciences) ;
  • Jafari, Sabah Kayvan (Department of Biology, Payame Noor University of Mashhad) ;
  • Firizi, Maryam Nezafat (Department of Pathobiology and Medical Laboratory Science, School of Medicine, North Khorasan University of Medical Sciences) ;
  • Abbaspour, Ali Reza (Department of Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences) ;
  • Gharib, Fahime Ghafoori (Department of Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences) ;
  • Ghobadi, Yusef (Department of Immunology, School of Medicine, Tarbiat Modares University) ;
  • Gholizadeh, Samira (Department of Immunology, School of Medicine, Tarbiat Modares University)
  • 투고 : 2015.11.29
  • 심사 : 2016.02.15
  • 발행 : 2016.03.31
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초록

Objective: In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. Methods: Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and $17{\beta}-estradiol$, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. Results: We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and $17{\beta}-estradiol$ levels, and a reduced frequency of macrophages and uNK cells. Conclusion: Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes.

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참고문헌

  1. Allen TK, Jones CA, Habib AS. Dexamethasone for the prophylaxis of postoperative nausea and vomiting associated with neuraxial morphine administration: a systematic review and meta-analysis. Anesth Analg 2012;114:813-22. https://doi.org/10.1213/ANE.0b013e318247f628
  2. Crowley P. Withdrawn: prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2007;(3):CD000065.
  3. Breton MC, Beauchesne MF, Lemiere C, Rey E, Forget A, Blais L. Risk of perinatal mortality associated with inhaled corticosteroid use for the treatment of asthma during pregnancy. J Allergy Clin Immunol 2010;126:772-7.e2. https://doi.org/10.1016/j.jaci.2010.08.018
  4. Adams Waldorf KM, Nelson JL. Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. Immunol Invest 2008;37:631-44. https://doi.org/10.1080/08820130802205886
  5. Lash GE, Bulmer JN, Innes BA, Drury JA, Robson SC, Quenby S. Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage. Angiogenesis 2011;14:523-32. https://doi.org/10.1007/s10456-011-9237-x
  6. Shaikh S, Verma H, Yadav N, Jauhari M, Bullangowda J. Applications of steroid in clinical practice: a review. Int Sch Res Notices 2012;2012:1-11. https://doi.org/10.1093/imrn/rnr003
  7. Michael AE, Papageorghiou AT. Potential significance of physiological and pharmacological glucocorticoids in early pregnancy. Hum Reprod Update 2008;14:497-517. https://doi.org/10.1093/humupd/dmn021
  8. Edwards HE, Burnham WM. The impact of corticosteroids on the developing animal. Pediatr Res 2001;50:433-40. https://doi.org/10.1203/00006450-200110000-00003
  9. Morrison JL, Botting KJ, Soo PS, McGillick EV, Hiscock J, Zhang S, et al. Antenatal steroids and the IUGR fetus: are exposure and physiological effects on the lung and cardiovascular system the same as in normally grown fetuses? J Pregnancy 2012;2012:839656.
  10. Zhu H, Hou CC, Luo LF, Hu YJ, Yang WX. Endometrial stromal cells and decidualized stromal cells: origins, transformation and functions. Gene 2014;551:1-14. https://doi.org/10.1016/j.gene.2014.08.047
  11. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update 2006;12:731-46. https://doi.org/10.1093/humupd/dml004
  12. Singh H, Aplin JD. Endometrial apical glycoproteomic analysis reveals roles for cadherin 6, desmoglein-2 and plexin b2 in epithelial integrity. Mol Hum Reprod 2015;21:81-94. https://doi.org/10.1093/molehr/gau087
  13. De Blasio MJ, Dodic M, Jefferies AJ, Moritz KM, Wintour EM, Owens JA. Maternal exposure to dexamethasone or cortisol in early pregnancy differentially alters insulin secretion and glucose homeostasis in adult male sheep offspring. Am J Physiol Endocrinol Metab 2007;293:E75-82. https://doi.org/10.1152/ajpendo.00689.2006
  14. Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev 2012;6:CD005996.
  15. Gur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study. Reprod Toxicol 2004;18:93-101. https://doi.org/10.1016/j.reprotox.2003.10.007
  16. Mwansa-Kambafwile J, Cousens S, Hansen T, Lawn JE. Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth. Int J Epidemiol 2010;39 Suppl 1:i122-33. https://doi.org/10.1093/ije/dyq029
  17. Glantz A, Marschall HU, Lammert F, Mattsson LA. Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. Hepatology 2005;42:1399-405. https://doi.org/10.1002/hep.20952
  18. Ostensen M, Khamashta M, Lockshin M, Parke A, Brucato A, Carp H, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther 2006;8:209. https://doi.org/10.1186/ar1957
  19. Xu T, Qiao J, Zhao L, He G, Li K, Wang J, et al. Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice. Eur Respir J 2009;33:852-60. https://doi.org/10.1183/09031936.00130507
  20. Clark DA, Petitbarat M, Chaouat G. How should data on murine spontaneous abortion rates be expressed and analyzed? Am J Reprod Immunol 2008;60:192-6. https://doi.org/10.1111/j.1600-0897.2008.00612.x
  21. Bibak B, Gharib FG, Daneshmandi S, Abbaspour AR, Firizi MN, Ahmadabad HN. The immunomodulatory effects of abortionprone mice decidual and serum soluble factors on macrophages and splenocytes. Eur J Obstet Gynecol Reprod Biol 2012;165:331-6. https://doi.org/10.1016/j.ejogrb.2012.08.006
  22. Wichtel JJ, Evans LE, Clark TL. Termination of midterm pregnancy in mares using intra-allantoic dexamethasone. Theriogenology 1988;29:1261-7. https://doi.org/10.1016/0093-691X(88)90006-4
  23. Zone M, Wanke M, Rebuelto M, Loza M, Mestre J, Duchene A, et al. Termination of pregnancy in dogs by oral administration of dexamethasone. Theriogenology 1995;43:487-94. https://doi.org/10.1016/0093-691X(94)00041-R
  24. van Mourik MS, Macklon NS, Heijnen CJ. Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment. J Leukoc Biol 2009;85:4-19.
  25. Piccinni MP. T cells in normal pregnancy and recurrent pregnancy loss. Reprod Biomed Online 2007;14 Spec No 1:95-9.
  26. Fahey AJ, Robins RA, Kindle KB, Heery DM, Constantinescu CS. Effects of glucocorticoids on STAT4 activation in human T cells are stimulus-dependent. J Leukoc Biol 2006;80:133-44. https://doi.org/10.1189/jlb.0605296
  27. Erlebacher A. Immunology of the maternal-fetal interface. Annu Rev Immunol 2013;31:387-411. https://doi.org/10.1146/annurev-immunol-032712-100003
  28. Ott TL, Kamat MM, Vasudevan S, Townson DH, Pate JL. Maternal immune responses to conceptus signals during early pregnancy in ruminants. Anim Reprod 2014;11:237-45.
  29. Arulkumaran S, Sivanesaratnam V, Chatterjee A, Kumar P. Essentials of obstetrics. London: Jaypee Brothers; 2004.
  30. Sowers JR, Rice BF, Blanchard S. Effect of dexamethsone on luteinizing hormone and follicle stimulating hormone responses to LHRH and to clomiphene in the follicular phase of women with normal menstrual cycles. Horm Metab Res 1979;11:478-80. https://doi.org/10.1055/s-0028-1092765
  31. Rosen H, Jameel ML, Barkan AL. Dexamethasone suppresses gonadotropin- releasing hormone (GnRH) secretion and has direct pituitary effects in male rats: differential regulation of GnRH receptor and gonadotropin responses to GnRH. Endocrinology 1988;122:2873-80. https://doi.org/10.1210/endo-122-6-2873
  32. Skalba P, Guz M. Hypogonadotropic hypogonadism in women. Endokrynol Pol 2011;62:560-7.
  33. Schumacher A, Costa SD, Zenclussen AC. Endocrine factors modulating immune responses in pregnancy. Front Immunol 2014;5:196.
  34. Robinson DP, Klein SL. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm Behav 2012;62:263-71. https://doi.org/10.1016/j.yhbeh.2012.02.023
  35. Moffett-King A. Natural killer cells and pregnancy. Nat Rev Immunol 2002;2:656-63. https://doi.org/10.1038/nri886
  36. Lombardelli L, Aguerre-Girr M, Logiodice F, Kullolli O, Casart Y, Polgar B, et al. HLA-G5 induces IL-4 secretion critical for successful pregnancy through differential expression of ILT2 receptor on decidual CD4+ T cells and macrophages. J Immunol 2013;191:3651-62. https://doi.org/10.4049/jimmunol.1300567
  37. Gao R, Chen L, Tan W, Tan H, Ou X, Li H, et al. Role of macrophages in mouse uterine during the peri-implantation period. Nan Fang Yi Ke Da Xue Xue Bao 2015;35:365-9.
  38. Hammer A. Immunological regulation of trophoblast invasion. J Reprod Immunol 2011;90:21-8. https://doi.org/10.1016/j.jri.2011.05.001
  39. Ashwell JD, Lu FW, Vacchio MS. Glucocorticoids in T cell development and function*. Annu Rev Immunol 2000;18:309-45. https://doi.org/10.1146/annurev.immunol.18.1.309
  40. Sugimoto Y, Ogawa M, Tai N, Kamei C. Inhibitory effects of glucocorticoids on rat eosinophil superoxide generation and chemotaxis. Int Immunopharmacol 2003;3:845-52. https://doi.org/10.1016/S1567-5769(03)00055-9
  41. DeLoia JA, Stewart-Akers AM, Brekosky J, Kubik CJ. Effects of exogenous estrogen on uterine leukocyte recruitment. Fertil Steril 2002;77:548-54. https://doi.org/10.1016/S0015-0282(01)03062-X
  42. Warning JC, McCracken SA, Morris JM. A balancing act: mechanisms by which the fetus avoids rejection by the maternal immune system. Reproduction 2011;141:715-24. https://doi.org/10.1530/REP-10-0360
  43. Smith SD, Dunk CE, Aplin JD, Harris LK, Jones RL. Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy. Am J Pathol 2009;174:1959-71. https://doi.org/10.2353/ajpath.2009.080995
  44. Dawes GS, Serra-Serra V, Moulden M, Redman CW. Dexamethasone and fetal heart rate variation. Br J Obstet Gynaecol 1994;101:675-9. https://doi.org/10.1111/j.1471-0528.1994.tb13183.x
  45. Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2013;8:CD006764.
  46. Derks JB, Mulder EJ, Visser GH. The effects of maternal betamethasone administration on the fetus. Br J Obstet Gynaecol 1995;102:40-6. https://doi.org/10.1111/j.1471-0528.1995.tb09024.x
  47. Dreger A, Feder EK, Tamar-Mattis A. Prenatal dexamethasone for congenital adrenal hyperplasia: an ethics canary in the modern medical mine. J Bioeth Inq 2012;9:277-94. https://doi.org/10.1007/s11673-012-9384-9
  48. Lee JY, Park SJ, Kim SH, Kim MH. Prenatal administration of dexamethasone during early pregnancy negatively affects placental development and function in mice. J Anim Sci 2012;90:4846-56. https://doi.org/10.2527/jas.2012-5090
  49. Newnham JP, Evans SF, Godfrey M, Huang W, Ikegami M, Jobe A. Maternal, but not fetal, administration of corticosteroids restricts fetal growth. J Matern Fetal Med 1999;8:81-7.
  50. Ain R, Canham LN, Soares MJ. Dexamethasone-induced intrauterine growth restriction impacts the placental prolactin family, insulin-like growth factor-II and the Akt signaling pathway. J Endocrinol 2005;185:253-63. https://doi.org/10.1677/joe.1.06039
  51. Care AS, Ingman WV, Moldenhauer LM, Jasper MJ, Robertson SA. Ovarian steroid hormone-regulated uterine remodeling occurs independently of macrophages in mice. Biol Reprod 2014;91:60.

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