References:
  1. Charach R, Sheiner E, Beharier O, Sergienko R, Kessous R. Recurrent pregnancy loss and future risk of female malignancies. Arc Gynecol Obstet. (2018) 298: 781-87.
  2. Ali S, Majid S, Ali MN, Taing S. Evaluation of T cell cytokines and their role in recurrent miscarriage. Int Immunopharmacol.(2020) 82: 106347. https://doi.org/10.1016/j.intimp.2020.106347
  3. Ghaebi M, Nouri M, Ghasemzadeh A, Farzadi L, Jadidi-Niaragh F, Ahmadi M, Yousefi M. Immune regulatory network in successful pregnancy and reproductive failures. Biomed Pharmacother. (2017) 88: 61-73.
  4. Williams Z. Inducing tolerance to pregnancy. N Engl J Med.(2012) 367:1159- 61.
  5. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT. Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T‐cell subset. Immunol. (2004) 112: 38-43.
  6. Zenclussen AC, Gerlof K, Zenclussen ML, Sollwedel A, Bertoja AZ, Ritter T, Kotsch K, Leber J, Volk HD. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+ CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am J Pathol. (2005) 166: 811-22.
  7. Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clin chim acta. (2011) 412: 702-8.
  8. Hamor C, Monsivais D, Matzuk M. Identifying the BMP Pathway Type II Receptors in Decidualization. The FASEB Journal . (2019) 33:476-9.
  9. Mori M, Bogdan A, Balassa T, Csabai T, Szekeres-Bartho J. The decidua—the maternal bed embracing the embryo—maintains the pregnancy. In Sem Immunopathol . (2016) 38: 635-49.
  10. Szwarc MM, Hai L, Gibbons WE, Mo Q, Lanz RB, DeMayo FJ, Lydon JP. Early growth response 1 transcriptionally primes the human endometrial stromal cell for decidualization. J Steroid Biochem Mol Biol.(2019)189: 283-90.
  11. Soczewski E, Grasso E, Gallino L, Hauk V, Fernández L, Gori S, Paparini D, Leirós CP, Ramhorst R. Immunoregulation of the decidualization program: focus on the endoplasmic reticulum stress.Reprod . (2020)159: R203-11.
  12. Lash GE, Ernerudh J. Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage. J Reprod Immunol. (2015) 108: 83-89.
  13. Tabibzadeh S. Human endometrium: an active site of cytokine production and action. Endocr Rev. (1991) 12: 272-90.
  14. Vignali D. How many mechanisms do regulatory T cells need? Eur J Immunol. (2008) 38:908–11.
  15. Liu J, Hao S, Chen X, Zhao H, Du L, Ren H, Wang C, Mao H. Human placental trophoblast cells contribute to maternal–fetal tolerance through expressing IL-35 and mediating iT R 35 conversion. Nat Comm. (2019) 10:1-0.
  16. Hinduja I, Pathare ADS, Zaveri K. Immunological approach of personalized treatment for recurrent implantation failure patients undergoing IVF. Glob J Reprod Med. (2018) 5.
  17. MUÑOZ OB, Martínez-Vega RA, Torres-Yepes K, Olivares EG Cytokine secretion by endometrial stromal human cells from menstruation and decidua stromal human cells from placentas collected of vaginal and caesarean deliveries. Front Immunol. (2015). doi: 10.3389/conf.fimmu.2015.05.00104
  18. Woodworth CD, Simpson S. Comparative lymphokine secretion by cul-tured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines. Am J Pathol. (1993)142: 1544-55.
  19. Fichorova RN, Anderson DJ. Differential expression of immunobiological mediators by immortalized human cervical and vaginal epithelial cells.Biol Reprod. (1999) 60: 508–14.
  20. Grant KS, Wira CR Effect of mouse uterine stromal cells on epithelial cell transepithelial resistance (TER) and TNFα and TGFβ release in culture. Biol Reprod. (2003) 69:1091–8.
  21. Fahey JV, Schaefer TM, Channon JY, Wira CR. Secretion of cytokines and chemokines by polarized human epithelial cells from the female reproductive tract. Hum Reprod. (2005) 20:1439-46.
  22. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. (1986) 136: 2348-57.
  23. Chaouat, G., Menu, E., Clark, D.A., Dy, M., Minkowski, M. and Wegmann,T.G. (1990) Control of fetal survival in CBA x DBA/2 mice bylymphokine therapy. J Reprod Fertil. (89) 447-58.
  24. Lin H, Mosmann MT, Guilbert L, Tuntipopipat S, Wegmann TG. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol. (1993) 151:4562-73.
  25. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternalfetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. (1993) 14:353-6.
  26. Lidstrom C, Matthiesen L, Berg G, Sharma S, Ernerudh J, Ekerfelt C: Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood: implications for suppressor macrophages in decidua. Am J Reprod Immunol. (2003) 50: 444– 52.
  27. Renaud SJ, Graham CH: The role of macrophages in utero‐placental interactions during normal and pathological pregnancy. Immunol Invest. (2008) 37: 535– 64.
  28. Lash GE, Robson SC, Bulmer JN: Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua.Placenta. (2010) 31 Suppl: S87–S92.
  29. Lee SK, Kim CJ, Kim DJ, Kang JH. Immune Cells in the Female Reproductive Tract. Immune Netw. (2015) 15: 16–26.
  30. Lee JY, Lee M, Lee SK. Role of Endometrial Immune Cells in Implantation. Clin Exp Reprod Med. (2011) 38:119–25.
  31. Harrity C, Bereir MM, Walsh DJ, Marron KD. Moving from Peripheral Blood to Local Uterine Immunophenotype Analysis in Patients with Poor Reproductive History: Pilot Study of a Novel Technique. Ir J Med Sci. (2019) 188: 893–901.
  32. Flynn L, Byrne B, Carton J, Kelehan P, O’Herlihy C, O’Farrelly C. Menstrual Cycle Dependent Fluctuations in NK and T-Lymphocyte Subsets from Non-Pregnant Human Endometrium. Am J Reprod Immunol.(2000) 43: 209–17.
  33. Lee S, Kim J, Jang B, Hur S, Jung U, Kil K, Na B, Lee M, Choi Y, Fukui A, Gilman-Sachs A. Fluctuation of peripheral blood T, B, and NK cells during a menstrual cycle of normal healthy women. J Immunol.(2010) 185:756-62
  34. Zenclussen AC, Hammerling GJ. Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation. Front Immunol. (2015) 6: 321.
  35. Salamonsen LA, Lathbury LJ. Endometrial Leukocytes and Menstruation.Hum Reprod Update. (2000) 6: 16–27.
  36. Robertson SA, Moldenhauer LM. Immunological Determinants of Implantation Success. Int J Dev Biol. (2014) 58: 205–17.
  37. King A. Uterine Leukocytes and Decidualization. Hum Reprod Update. (2000) 6:28–36.
  38. Schulke L, Manconi F, Markham R, Fraser IS. Endometrial Dendritic Cell Populations During the Normal Menstrual Cycle. Hum Reprod.(2008) 23: 1574–80
  39. Ramhorst R, Grasso E, Paparini D, Hauk V, Gallino L, Calo G, Vota D, Perez Leiros C. Decoding the Chemokine Network that Links Leukocytes with Decidual Cells and the Trophoblast During Early Implantation.Cell Adh Migr. (2016) 10: 197–207.
  40. Rieger L, Honig A, Sutterlin M, Kapp M Dietl J, Ruck P, Kammerer U. Antigen-Presenting Cells in Human Endometrium During the Menstrual Cycle Compared to Early Pregnancy. J Soc Gynecol Invest. (2004) 11: 488–93
  41. Maridas DE, Hey-Cunningham AJ, Ng CHM, Markham R, Fraser IS, Berbic M. Peripheral and Endometrial Dendritic Cell Populations During the Normal Cycle and in the Presence of Endometriosis. J Endometr Pelvic Pain Disord. (2014) 6: 67–119.
  42. Zenclussen AC, Olivieri DN, Dustin ML, Tadokoro CE. In Vivo Multiphoton Microscopy Technique to Reveal the Physiology of the Mouse Uterus. Am J Reprod Immunol. (2013) 69: 281–89.
  43. Okada H, Tsuzuki T, Murata H. Decidualization of the Human Endometrium. Reprod Med Biol. (2018) 17: 220–27.
  44. Drury JA, Parkin KL, Coyne L, Giuliani E, Fazleabas AT, Hapangama DK. The Dynamic Changes in the Number of Uterine Natural Killer Cells are Specific to the Eutopic but not to the Ectopic Endometrium in Women and in a Baboon Model of Endometriosis. Reprod Biol Endocrinol.(2018) 16: 67.
  45. Manaster I, Mizrahi S, Goldman-Wohl D, Sela HY Stern-Ginossar N, Lankry D, Gruda R, Hurwitz A, Bdolah Y, Haimov-Kochman R, et al. Endometrial NK Cells are Special Immature Cells that Await Pregnancy.J Immunol. (2008) 181: 1869–76.
  46. Fukui A, Funamizu A, Fukuhara R, Shibahara H. Expression of Natural Cytotoxicity Receptors and Cytokine Production on Endometrial Natural Killer Cells in Women with Recurrent Pregnancy Loss or Implantation Failure, and the Expression of Natural Cytotoxicity Receptors on Peripheral Blood Natural Killer Cells in Pregnant Women with a History of Recurrent Pregnancy Loss. J Obstet Gynaecol Res. (2017) 43: 1678–86
  47. Chang HF, Bzeih H, Chitirala P, Ravichandran K, Sleiman M, Krause E, Hahn U, Pattu V, Rettig J. Preparing the Lethal Hit: Interplay Between Exo-And Endocytic Pathways in Cytotoxic T Lymphocytes. Cell Mol Life Sci. (2017) 74: 399–408
  48. Zhao X, Jiang Y, Wang L, Li Z, Li Q, Feng X. Advances in Understanding the Immune Imbalance between T-Lymphocyte Subsets and NK Cells in Recurrent Spontaneous Abortion. Geburtshilfe Frauenheilkd.(2018) 78: 677–83.
  49. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and Peripheral Blood CD4+CD25+ Regulatory T Cells in Early Pregnancy Subjects and Spontaneous Abortion Cases. Mol Hum Reprod. (2004) 10:347–53.
  50. Roberton SA, Care AS, Moldenhauer LM. Regulatory T Cells in Embryo Implantation and the Immune Response to Pregnancy. J Clin Invest . (2018) 128: 4224–35.
  51. Alijotas-Reig J, Llurba E, Gris JM. Potentiating Maternal Immune Tolerance in Pregnancy: A New Challenging Role for Regulatory T Cells.Placenta. (2014) 35: 241–48.
  52. Arruvito L, Sanz M, Banham AH, Fainboim L. Expansion of CD4+CD25+and FOXP3+Regulatory T Cells During the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction. J Immunol. (2007) 178: 2572–78.
  53. Kofod L, Lindhard A, Hviid TVF. Implications of Uterine NK Cells and Regulatory T Cells in the Endometrium of Infertile Women. Hum Immunol. (2018) 79: 693–701
  54. Vanderstraeten A, Tuyaerts S, Amant F. The Immune System in the Normal Endometrium and Implications for Endometrial Cancer Development.J Reprod Immunol. (2015) 109: 7–16.
  55. Nadkarni S, Smith J, Sferruzzi-Perri AN, Ledwozyw A, Kishore M, Haas R, Mauro C, Williams DJ, Farsky SHP, Marelli-Berg FM, et al. Neutrophils Induce Proangiogenic T Cells with a Regulatory Phenotype in Pregnancy. Proc Natl Acad Sci. USA (2016) 113: E8415–E8424
  56. King AE, Critchley HOD, Kelly RW. Innate Immune Defences in the Human Endometrium. Reprod Biol Endocrinol. (2003) 1: 116.
  57. Armstrong GM, Maybin JA, Murray AA, Nicol M, Walker C, Saunders PTK, Rossi AG, Critchley HOD. Endometrial Apoptosis and Neutrophil Infiltration During Menstruation Exhibits Spatial and Temporal Dynamics that are Recapitulated in a Mouse Model. Sci Rep.(2017) 12:17416
  58. Faas MM, De Vos P. Innate Immune Cells in the Placental Bed in Healthy Pregnancy and Preeclampsia. Placenta ( 2018) 69:125–33.
  59. Tsao FY, Wu MY, Chang YL, Wu CT, Ho HN. M1 Macrophages Decrease in the Deciduae from Normal Pregnancies but not from Spontaneous Abortions or Unexplained Recurrent Spontaneous Abortions. J Formos Med Assoc. (2018) 117, 204–11.
  60. Erlebacher A. Immunology of the Maternal-Fetal Interface. Annu Rev Immunol. (2013) 31: 387–411.
  61. Care AS, Diener KR, Jasper MJ, Brown HM, Ingman WV, Robertson SA. Macrophages Regulate Corpus Luteum Development During Embryo Implantation in Mice. J Clin Invest. (2013) 123: 3472–87.
  62. Jeziorska M, Salamonsen LA, Woolley DE. Mast Cell and Eosinophil Distribution and Activation in Human Endometrium Throughout the Menstrual Cycle. Biol Reprod. (1995) 53: 312–20.
  63. De Leo B, Esnal-Zufiaurre A, Collins F, Critchley HOD, Saunders PTK. Immunoprofiling of Human Uterine Mast Cells Identifies Three Phenotypes and Expression of ERβ and Glucocorticoid Receptor.F1000Res. (2017) 6: 667.
  64. Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA. Interferon gamma in successful pregnancies. Biol Reprod. (2009) 80: 848-59.
  65. Piccinni MP, Scaletti C, Maggi E, Romagnani S. Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol. (2000) 109: 30-3.
  66. Drake PM, Gunn MD, Charo IF, Tsou CL, Zhou Y, Huang L, Fisher SJ. Human placental cytotrophoblasts attract monocytes and CD56 (bright) natural killer cells via the actions of monocyte inflammatory protein 1alpha. J Exp Med. (2001) 193: 1199-1212.
  67. Dimitriadis E, White CA, Jones RL, Salamonsen LA. Cytokines, chemokines and growth factors in endometrium related to implantation.Hum Reprod Update. (2005) 11: 613-30.
  68. Lash GE, Schiessl B, Kirkley M, Innes BA, Cooper A, Searle RF, Robson SC, Bulmer JN. Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy. J Leukoc Biol.(2006) 80: 572-80.
  69. Aplin JD. The cell biological basis of human implantation. Best Pract Res Clin Obstet Gynaecol . (2000) 14: 757-64.
  70. Van Mourik MSK, Macklon NS, Heijnen CJ. Embryonic implantation: cytokines, adhesion molecules and immune cells in establishing an implantation environment. J Leukocyt Biol. (2009) 85:4-19.
  71. Romagnani S. Human Th1 and Th2: doubt no more. Immunol Today.(1991) 12:256-7.
  72. Erdmann AA, Jung U, Foley JE, Toda Y, Fowler DH. Co-stimulated/Tc2 cells abrogate murine marrow graft rejection. Biol Blood Marrow Transp. (2004) 10: 604-13.
  73. Burns WR, Wang Y, Tang PC, Ranjbaran H, Iakimov A, Kim J, Cuffy M, Bai Y, Pober JS, Tellides G. Recruitment of CXCR3+ and CCR5+ T Cells and Production of Interferon‐γ‐Inducible Chemokines in Rejecting Human Arteries. Am J Transp. (2005) 5:1226-36.
  74. Nickerson P, Steurer W, Steiger J, Zheng X, Steele AW, Strom TB. Cytokines and the Th1/Th2 paradigm in transplantation. Curr Opin Immunol. (1994) 6:757-64.
  75. Strom TB, Roy-Chaudhury P, Manfro R, Xheng XX, Nickerson PW, Wood K, Bushell A. The Th1/Th2 paradigm and the allograft response. Curr Opin Immunol. (1996) 8:688-93.
  76. Li XC, Zand MS, Li Y, Zheng XX, StromTB. On histocompatibility barriers, Th1 to Th2 immune deviation, and the nature of the allograft responses. J Immunol .(1998) 161:2241-7
  77. Ashkar AA, Di Santo JP, Croy BA. Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy.J Exp Med. (2000) 192: 259-70.
  78. Croy BA, Esadeg S, Chantakru S, Van Den Heuvel M, Paffaro VA, He H, Black GP, Ashkar AA, Kiso Y, Zhang J. Update on pathways regulating the activation of uterine Natural Killer cells, their interactions with decidual spiral arteries and homing of their precursors to the uterus. J Reprod Immunol. (2003) 59: 175-91.
  79. Robson A, Harris LK, Innes BA, Lash GE, Aljunaidy MM, Aplin JD, Baker PN, Robson SC, Bulmer JN. Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. FASEB J. (2012) 26: 4876-85.
  80. Fallon PG, Jolin HE, Smith P, Emson CL, Townsend MJ, Fallon R, Smith P, McKenzie AN. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity. (2002) 17:7-17.
  81. Saito S, Nakashima A, Shima T, Ito M. Th1Th2Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol . (2010) 63: 601-10
  82. 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) 4:1020-24.
  83. Raghupathy R. Th1-type immunity is incompatible with successful pregnancy. Immunol Today. (1997) 18:478-82.
  84. Chaouat G, Lédée‐Bataille N, Zourbas S, Ostojic S, Dubanchet S, Martal J, Frydman R. Cytokines, implantation and early abortion: re‐examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept. Am J Reprod Immunol . (2003) 50:177-86.
  85. Bates MD, Quenby S, Takakuwa K, Johnson PM, Vince GS. Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss? Hum Reprod. (2002) 17:2439-44.
  86. Chaouat G, Zourbas S, Ostojic S, Lappree-Delage G, Dubanchet S, Ledee N, Martal J. A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Th1/Th2 dichotomy. J Reprod Immunol. (2002) 53: 241-56.
  87. Peck A, Mellins ED. Plasticity of T-cell phenotype and function: the T helper type 17 example. Immunol. (2010) 129:147-53.
  88. Crome SQ, Wang AY, Levings MK. Translational mini-review series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol. (2010) 159:109-19.
  89. Lee SK, Kim JY, Lee M, Gilman Sachs A, Kwak Kim J. Th17 and regulatory T cells in women with recurrent pregnancy loss. Am J Reprod Immunol . (2012) 67: 311-8.
  90. Steinborn A, Schmitt E, Kisielewicz A, Rechenberg S, Seissler N, Mahnke K, Schaier M, Zeier M, Sohn C. Pregnancy associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs. Clin Exp Immunol. ( 2012) 167: 84-98.
  91. Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD. The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Hum Reprod. (2010) 25: 2591-6.
  92. Corthay A. How do regulatory T cells work? Scand J Immunol.(2009) 70: 326-36.
  93. Saito S, Sasaki Y, Sakai M. CD4 (+) CD25 high regulatory T cells in human pregnancy. J Reprod Immunol. ( 2005) 65: 111-20.
  94. Keller CC, Eikmans M, van der Hoorn ML, Lashley LE. Recurrent miscarriages and the association with regulatory T cells; a systematic review. J Reprod Immunol. (2020) 103105.
  95. Ruocco MG, Chaouat G, Florez L, Bensussan A, Klatzmann D. Regulatory T-cells in pregnancy: historical perspective, state of the art, and burning questions. Front Immunol. (2014) 5 : 389, doi:10.3389/fimmu.2014.00389
  96. Erlebacher A. Mechanisms of T cell tolerance towards the allogeneic fetus. Nat Rev Immunol. (2013) 13:23–33.
  97. Robertson SA, Prins JR, Sharkey DJ, Moldenhauer LM. Seminal fluid and the generation of regulatory T cells for embryo implantation. Am J Reprod Immunol. ( 2013) 69: 315–30.
  98. Zenclussen AC. Adaptive immune responses during pregnancy. Am J Reprod Immunol. (2013) 69:291–303.
  99. Prabhu Das M, Bonney E, Caron K, Dey SCA, Fazleabas A, et al. Immune mechanisms at the maternal-fetal interface: perspectives and challenges. Nat Immunol. (2015) 16:328–34.
  100. Saito S, Nakabayashi Y, Nakashima A, Shima T, Yoshino O. A new era in reproductive medicine: consequences of third-party oocyte donation for maternal and fetal health. Semin Immunopathol. (2016) 38:687–97.
  101. Saito S, Shima T, Nakashima A, Inada K, Yoshino O. Role of paternal antigen-specific treg cells in successful implantation. Am J Reprod Immunol. (2016) 75:310–6.
  102. Wang WJ, Hao CF, Yin GJ, Bao SH, Qiu LH, Lin QD. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol. (2010) 84:164-70.
  103. Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S. Accumulation of IL-17-positive cells in decidua of inevitable abortion cases.Am J Reprod Immunol. (2010) 64:4-11.
  104. Wu HX, Jin LP, Xu B, Liang SS, Li DJ. Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17. CellMol Immunol. (2014) 11: 253-62.
  105. Liu YS, Wu L, Tong XH, Wu LM, He GP, Zhou GX, Luan HB. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol . (2011) 65: 503–11.
  106. Abdolmohammadi Vahid S, Ghaebi M, Ahmadi M, Nouri M, Danaei S, Aghebati‐Maleki L, Mousavi Ardehaie R, Yousefi B, Hakimi P, Hojjat‐Farsangi M, Rikhtegar R. Altered T‐cell subpopulations in recurrent pregnancy loss patients with cellular immune abnormalities.J Cellul Physiol. (2019): 234:4924-33.
  107. Raghupathy R, Makhseed M, Azizieh F, Hassan N, Al-Azemi M, Al-Shamali E. Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions. Cell Immunol. (1999) 196:122–30. 10.1006/cimm.1999.1532
  108. Kwak JY, Beaman KD, Gilman-Sachs A, Ruiz J, Shewitz D, Beer AE,. Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses. Am J Reprod. Immunol. (1995) 34: 93–99.
  109. Kwak‐Kim JY, Chung‐Bang HS, Ng SC, Ntrivalas EI, Mangubat CP, Beaman KD, Beer AE, Gilman‐Sachs A. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod. (2003)18:767-73.
  110. Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM. The immunology of successful pregnancy. Hum Reprod Update . (2003) 9: 347–57.
  111. Beer AE, Kwak JY, Ruiz JE. Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failed in vitro fertilization cycles.Am Reprod Immunol. (1996) 35: 376–82.
  112. Ruiz JE, Kwak JY, Baum L, Gilman-Sachs A, Beaman KD, Kim YB, Beer AE. Intravenous immunoglobulin inhibits natural killer cell activity in vivo in women with recurrent spontaneous abortion. Am J Reprod Immunol. (1996) 35: 370–75.
  113. Dong P, Wen X, Liu J, Yan CY, Yuan J, Luo LR, Hu QF, Li J. Simultaneous detection of decidual Th1/Th2 and NK1/NK2 immunophenotyping in unknown recurrent miscarriage using 8-color flow cytometry with FSC/Vt extended strategy. Biosc Rep. (2017) 37.
  114. Yuan J, Li J, Huang SY, Sun X. Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion. J Reprod Immunol. (2015) 110:81-8.
  115. Sereshki N, Gharagozloo M, Ostadi V, Ghahiri A, Roghaei MA, Mehrabian F, Andalib AA, Hassanzadeh A, Hosseini H, Rezaei A. Variations in T-helper 17 and regulatory T cells during the menstrual cycle in peripheral blood of women with recurrent spontaneous abortion.Int J Fertil Steril. (2014) 8:59.
  116. Deshmukh H, Way SS. Immunological basis for recurrent fetal loss and pregnancy complications. Annual Review of Pathology: Mech Dis. (2019)14:185-210.
  117. Brosens JJ, Pijnenborg R, Brosens IA. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol. (2002) 187: 1416-23.
  118. Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev.(2014) 35: 851-905.
  119. Vinketova K, Mourdjeva M, Oreshkova T. Human decidual stromal cells as a component of the implantation niche and a modulator of maternal immunity. J Preg. (2016) 2016: 1-17.
  120. Brosens JJ. Gellersen B. Death or survival—progesterone-dependent cell fate decisions in the human endometrial stroma. J Mol Endocrinol . (2006) 36: 389-98.
  121. Maldonado-P´erez D, Evans J, Denison F, Millar RP, Jabbour HN. Potential roles of the prokineticins in reproduction. Trends Endocrinol Metabol . (2007) 18: 66-72.
  122. Schumacher A, Costa SD, Zenclussen AC. Endocrine factors modulating immune responses in pregnancy. Front Immunol . (2014) 5:196.
  123. Santner‐Nanan B, Peek MJ, Khanam R, Richarts L, Zhu E, Fazekas de St Groth B, Nanan R: Systemic increase in the ratio between Foxp3+ and IL‐17‐producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. (2009) 183: 7023– 30.
  124. Nakashima A, Ito M, Yoneda S, Shiozaki A, Hidaka T, Saito S: Circulating and decidual Th17 cell levels in healthy pregnancy.Am J Reprod Immunol. (2010) 63: 104– 9.
  125. Toldi G, Molvarec A, Stenczer B, Muller V, Eszes N, Bohacs A, Bikov A, Rigo J Jr, Vasarhelyi B, Losonczy G, Tamasi L: Peripheral Th1/Th2/Th17/regulatory T‐cell balance in asthmatic pregnancy.Int Immunol. (2011) 23: 669– 77.
  126. Berbic M, Hey‐Cunningham AJ, Ng C, Tokushige N, Ganewatta S, Markham R, Russell P, Fraser IS: The role of Foxp3+ regulatory T‐cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition. Hum Reprod. (2010) 25: 900– 7.
  127. Xiong H, Zhou C, Qi G: Proportional changes of CD4+CD25+Foxp3+ regulatory T cells in maternal peripheral blood during pregnancy and labor at term and preterm. Clin Invest Med. ( 2010) 33: E422.
  128. Steinborn A, Haensch GM, Mahnke K, Schmitt E, Toermer A, Meuer S, Sohn C: Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia? Clinical Immunol . (2008) 129: 401– 12
  129. Toldi G, Rigo J Jr, Stenczer B, Vasarhelyi B, Molvarec A: Increased prevalence of IL‐17‐producing peripheral blood lymphocytes in pre‐eclampsia. Am J Reprod Immunol (2011) 66: 223– 229.
  130. Hanna J, Goldman-Wohl D, Hamani Y, et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.Nat Med. (2006) 12: 1065–74.
  131. Quenby S, Nik H, Innes B, et al. Uterine natural killer cells and angiogenesis in recurrent reproductive failure. Hum Reprod. (2009) 24: 45–54.
  132. Godbole G, Modi D. Regulation of decidualization, interleukin-11 and interleukin-15 by homeobox A 10 in endometrial stromal cells. J Reprod Immunol. (2010) 85: 130–39.
  133. Ashkar AA, Black GP, Wei QX, et al. Assessment of requirements for IL-15 and IFN regulatory factors in uterine NK cell differentiation and function during pregnancy. J Immunol. ( 2003) 171: 2937–44.
  134. Kuroda K. Impaired endometrial function and unexplained recurrent pregnancy loss. Hypert Res Preg. (2019):HRP2018-012.
  135. Nallasamy S, Kaya Okur HS, Bhurke A, Davila J, Li Q, Young SL, Taylor RN, Bagchi MK, Bagchi IC. Msx homeobox genes act downstream of BMP2 to regulate endometrial decidualization in mice and in humans.Endocrinol . (2019) 160: 1631-44.
  136. Su Y, Guo S, Liu C, Li N, Zhang S, Ding Y, Chen X, He J, Liu X, Wang Y, Gao R. Endometrial pyruvate kinase M2 is essential for decidualization during early pregnancy. J Endocrinol. (2020) 1(aop).
  137. Neff AM, Yu J, Taylor RN, Bagchi IC, Bagchi MK. Insulin signaling via progesterone-regulated insulin receptor substrate 2 is critical for human uterine decidualization. Endocrinol. (2020) 161:bqz021.
  138. Yang Y, Zhang D, Qin H, Liu S, Yan Q. poFUT1 promotes endometrial decidualization by enhancing the O-fucosylation of Notch1.EBioMed . (2019) 44: 563-73.
  139. Oestreich AK, Chadchan SB, Popli P, Medvedeva A, Rowen MN, Stephens CS, Xu R, Lydon JP, Demayo FJ, Jungheim ES, Moley KH. The autophagy gene Atg16L1 is necessary for endometrial decidualization.Endocrinol. (2020) 161:bqz039.
  140. Tamura I, Takagi H, Doi-Tanaka Y, Shirafuta Y, Mihara Y, Shinagawa M, Maekawa R, Taketani T, Sato S, Tamura H, Sugino N. Wilms tumor 1 regulates lipid accumulation in human endometrial stromal cells during decidualization. J Biol Chem. (2020) 295:4673-83.
  141. Berkhout RP, Lambalk CB, Repping S, Hamer G, Mastenbroek S. Premature expression of the decidualization marker prolactin is associated with repeated implantation failure. Gynecol Endocrinol . (2019) :1-5.
  142. Oestreich AK, Chadchan SB, Medvedeva A, Lydon JP, Jungheim ES, Moley KH, Kommagani R. The autophagy protein, FIP200 (RB1CC1) mediates progesterone responses governing uterine receptivity and decidualization. Biol Reprod. (2020).
  143. Chobotova K, Karpovich N, Carver J, Manek S, Gullick WJ, Barlow DH, Mardon HJ. Heparin-binding epidermal growth factor and its receptors mediate decidualization and potentiate survival of human endometrial stromal cells. J Clin Endocrinol Metabol. (2005) 90:913-9.
  144. Tan Y, Li M, Cox S, Davis MK, Tawfik O, Paria BC, Das SK. HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation. Develop Biol. (2004) 265:181-95.
  145. Xie H, Wang H, Tranguch S, Iwamoto R, Mekada E, DeMayo FJ, Lydon JP, Das SK, Dey SK. Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Proceed National Acad Sci. (2007) 104:18315-20.
  146. Yu HF, Duan CC, Yang ZQ, Wang YS, Yue ZP, Guo B. HB-EGF Ameliorates Oxidative Stress-Mediated Uterine Decidualization Damage. Oxidat Med Cellul Longev. (2019) 2019.
  147. Babayev SN, Kanchwala M, Xing C, Akgul Y, Carr BR, Word RA. Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization. Reprod Sci. (2019) 26 :278-88.
  148. Mei J, Yan Y, Li SY, Zhou WJ, Zhang Q, Li MQ, Sun HX. CXCL16/CXCR6 interaction promotes endometrial decidualization via the PI3K/AKT pathway. Reprod. (2019)157:273-82.
  149. Jiang Y, Li J, Li G, Lin X, He Y, Lu J, Zhang Y, Wu J, Yang Z, Jiang Y, Wang H. Osteoprotegerin (OPG) Interacts with Syndecan-1 to Mediate Human Endometrial Stromal Decidualization via Decreasing Akt Phosphorylation. (2019).
  150. Lv S, Wang N, Ma J, Li WP, Chen ZJ, Zhang C. Impaired decidualization caused by downregulation of circadian clock gene BMAL1 contributes to human recurrent miscarriage. Biol Reprod. (2019) 101:138-47.
  151. Vallejo G, Mestre‐Citrinovitz AC, Winterhager E, Saragüeta PE. CSDC2, a cold shock domain RNA‐binding protein in decidualization. J Cellul Physiol . (2019) 234:740-8.
  152. Xu Y, Lu J, Wu J, Jiang R, Guo C, Tang Y, Wang H, Kong S, Wang S. HOXA10 co-factor MEIS1 is Required for the Decidualization in Human Endometrial Stromal Cell. J Mol Endocrinol. (2020) 1.
  153. Garrido-Gomez T, Quiñonero A, Dominguez F, Rubert L, Perales A, Hajjar KA, Simon C. Preeclampsia: a defect in decidualization is associated with deficiency of Annexin A2. Am J Obstet Gynecol. (2019).
  154. Windsperger K, Dekan S, Pils S, Golletz C, Kunihs V, Fiala C, Kristiansen G, Knöfler M, Pollheimer J. Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions. Hum Reprod.(2017) 32:1208-17.
  155. Pan-Castillo B, Gazze SA, Thomas S, Lucas C, Margarit L, Gonzalez D, Francis LW, Conlan RS. Morphophysical dynamics of human endometrial cells during decidualization. Nanomed: Nanotechnol Biol and Med. (2018) 14: 2235-45.
  156. Brar AK, Handwerger S, Kessler CA, Aronow BJ. Gene induction and categorical reprogramming during in vitro human endometrial fibroblast Decidualization. Physiol Genom. (2001) 7:135-48.
  157. Evans J, Catalano RD, Morgan K, Critchley HOD, Millar RP, Jabbour HN. Prokineticin 1 signaling and gene regulation in early human pregnancy.Endocrinol. (2008) 149:2877-87.
  158. Takano M, Lu Z, Goto T, Fusi L, Higham J, Francis J, Withey A, Hardt J, Cloke B, Stavropoulou AV, Ishihara O. Transcriptional cross talk between the forkhead transcription factor forkhead box O1A and the progesterone receptor coordinates cell cycle regulation and differentiation in human endometrial stromal cells. Mol Endocrinol. (2007) 21: 2334-49.
  159. Garrido-Gomez T, Dominguez F, Lopez JA, Camafeita E, Quiñonero A, Martinez-Conejero JA, Pellicer A, Conesa A, Simón C. Modeling human endometrial decidualization from the interaction between proteome and secretome. J Clin Endocrinol Metabol . (2011) 96:706-16.
  160. Popovici RM, Kao LC, Giudice LC. Discovery of new inducible genes in invitro decidualized human endometrial stromal cells using microarray technology. Endocrinol. (2000) 141: 3510-3.
  161. Krieg S, Westphal L. Immune function and recurrent pregnancy loss.Semin Reprod Med. (2015) 33:305-12.
  162. Lowe JS, Anderson PG. Stevens & Lowe’s Human Histology E-Book.Elsev Heal Sci. (2014).
  163. Das SK. Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reprod. (2009) 137:889-99.
  164. Ma X, Gao F, Rusie A, Hemingway J, Ostmann AB, Sroga JM, Jegga AG, Das SK. Decidual cell polyploidization necessitates mitochondrial activity. PLoS One. (2011) 6: 1-17.
  165. Dimitriadis E, Robb L, Salamonsen LA. Interleukin 11 advances progesterone-induced decidualization of human endometrial stromal cells. Mol Hum Reprod. (2002) 8: 636-43.
  166. Marwood M, Visser K, Salamonsen LA, Dimitriadis E. Interleukin-11 and leukemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications infertility regulation.Endocrinol. (2009) 150:2915-23.
  167. Paiva P, Salamonsen LA, Manuelpillaietal U. Interleukin11 promotes migration, but not proliferation, of human trophoblast cells, implying a role in placentation. Endocrinol. (2007) 148: 5566-72.
  168. Cook IH, Evans J, Maldonado-Perez D, Critchley HO, Sales KJ, Jabbour HN. Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway. Mol Hum Reprod . (2009) 16:158-69.
  169. Menkhorst E, Salamonsen LA, Zhang J, Harrison CA, Gu J, Dimitriadis E. Interleukin 11 and activin A synergise to regulate progesterone-induced but not cAMP-induced Decidualization. J Reprod Immunol . (2010) 84:124-32.
  170. Dimitriadis E, Stoikos C, Baca M, Fairlie WD, McCoubrie JE, Salamonsen LA. Relaxin and prostagland in E2 regulate interleukin 11 during human endometrial stromal cell Decidualization. J Clin Endocrinol Metabol . (2005) 90:3458–65.
  171. Lucas ES, Vrljicak P, Muter J, Diniz-da-Costa MM, Brighton PJ, Kong CS, Lipecki J, Fishwick KJ, Odendaal J, Ewington LJ, Quenby S. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Bio.(2020) 3:1-4.
  172. Robb L, Li R, Hartley L, Nandurkar HH, Koentgen F, Begley CG. Infertility in female mice lacking the receptor for interleukin 11 is due to a defective uterine response to implantation. Nat Med.(1998) 4:303-8.
  173. Bilinski P, Roopenian D, Gossler A. Maternal IL-11Ralpha function is required for normal decidua and feto-placental development in mice. Genes Dev.1998; 12:2234-43.
  174. Alexander CM, Hansell EJ, Behrendtsen O et al. Expression and function of matrix metalloproteinases and their inhibitors at the materno±embryonic boundary during mouse embryo implantation.Develop. (1996) 122:1723-36.
  175. Behrendtsen O, Alexander CM, Werb Z. Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths. Develop. ( 1992) 114:447-56.
  176. Zourbas S, Dubanchet S, Martal J, Chaouat G. Localization of pro‐inflammatory (IL‐12, IL‐15) and anti‐inflammatory (IL‐11, IL‐13) cytokines at the foetomaternal interface during murine pregnancy.Clin Exper Immunol. (2001) 126:519-28.
  177. Karpovich N, Klemmt P, Hwang JH, McVeigh JE, Heath JK, Barlow DH, Mardon HJ. The production of interleukin-11 and decidualization are compromised in endometrial stromal cells derived from patients with infertility. J Clin Endocrinol Metabol. (2005) 90: 1607-12.
  178. Dimitriadis E, Robb L, Liu YX, Enders AC, Martin H, Stoikos C, Wallace E, Salamonsen LA. IL-11 and IL-11Rα immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development. Reprod Bio Endocrinol. (2003)1:34.
  179. Chen HF, Lin CY, Chao KH, Wu MY, Yang YS, Ho HN. Defective production of interleukin-11 by decidua and chorionic villi in human anembryonic pregnancy. J Clin Endocrinol Metabol. ( 2002) 87: 2320-28.
  180. Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. (2012) 18:1754-67.
  181. Yeh CC, Chao KC, Huang SJ. Innate immunity, decidual cells, and preeclampsia. Reprod Sci. (2013) 20:339-53.
  182. Miyazaki S, Tanebe K, Sakai M et al. Interleukin 2 receptor gamma chain (γc) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise. Am J Reprod Immunol. (2002) 47: 222–30.
  183. Dunn CL, Kelly RW, Critchley HO. Decidualization of the human endometrial stromal cell: an enigmatic transformation. Reprod Biomed Online. (2003) 7:151-61.
  184. Kitaya K, Yasuda J, Yagi I et al. IL-15 expression at human endometrium and decidua. Bio Reprod. (2000) 63: 683–87.
  185. Lessey BA, Young SL. Structure, function, and evaluation of the female reproductive tract. In Yen and Jaffe’s Reprod . (2019): pp. 206-47.
  186. Miravet-Valenciano J, Ruiz-Alonso M, Simón C. Transcriptomics of the Human Endometrium and Embryo Implantation. In Hum Reprod Pren Genet. (2019): pp. 271-91. Academic Press.
  187. Lim KJ, Odukoya OA, Ajjan RA, Li TC, Weetman AP, Cooke ID. The role of T-helper cytokines in human reproduction. Fertil Steril. (2000) 73:136-42.
  188. King K, Smith S, Chapman M, Sacks G. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage.Hum Reprod. (2010) 251:52–8.
  189. Hutter S, Heublein S, Knabl J, Andergassen U, Vrekoussis T, Makrigiannakis A, et al. Macrophages: are they involved in endometriosis, abortion and preeclampsia and how? J Nippon Med Sch . (2013) 802:97–103. 10.1272/jnms.80.97
  190. Guenther S, Vrekoussis T, Heublein S, Bayer B, Anz D, Knabl J, et al. Decidual macrophages are significantly increased in spontaneous miscarriages and over-express FasL: a potential role for macrophages in trophoblast apoptosis. Int J Mol Sci. (2012) 137:9069–80.
  191. Bao SH, Wang XP, De Lin Q, Wang WJ, Yin GJ, Qiu LH. Decidual CD4+CD25+CD127dim/- regulatory T cells in patients with unexplained recurrent spontaneous miscarriage. Eur J Obstet Gynecol Reprod Biol. (2011) 1551:94–8.
  192. Osborne LM, Brar A, Klein SL. The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders.Brain Behav Immun. (2019) 76:7–16.
  193. Qian J, Zhang N, Lin J, Wang C, Pan X, Chen L, Li D, Wang L. Distinct Pattern of Th17/Treg Cells in Pregnant Women with a History of Unexplained Recurrent Spontaneous Abortion. Biosci Tren. (2018) 12: 157–67.
  194. Saifi B, Rezaee SA, Tajik N, Ahmadpour ME, Ashrafi M, Vakili R, SoleimaniAsl S, Aflatoonian R, Mehdizadeh M. Th17 Cells and Related Cytokines in Unexplained Recurrent Spontaneous Miscarriage at the Implantation Window. Reprod Biomed Online. (2014) 29: 481–9
  195. Zhang XX, Kang XM, Zhao AM. Regulation of CD4+FOXP3+T Cells by CCL20/CCR6 Axis in Early Unexplained Recurrent Miscarriage Patients.Genet Mol Res. (2015) 14: 9145–54.
  196. Wu M, Liu P, Cheng L. Galectin-1 Reduction and Changes in T Regulatory Cells May Play Crucial Roles in Patients with Unexplained Recurrent Spontaneous Abortion. Int J Clin Exp Pathol. (2015) 8: 1973–8.
  197. Inada K, Shima T, Ito M, Ushijima A, Saito S. Helios-Positive Functional Regulatory T Cells are Decreased in Decidua of Miscarriage Cases with Normal Fetal Chromosomal Content. J Reprod Immunol.(2015) 107: 10–19.
  198. Qian ZD, Huang LL, Zhu XM. An immunohistochemical study of CD83- and CD1a-positive dendritic cells in the decidua of women with recurrent spontaneous abortion. Eur J Med Res . (2015) 20:2.
  199. Askelund K, Liddell HS, Zanderigo AM, Fernando NS, Khong TY, Stone PR, Chamley LW. CD83(+)Dendritic Cells in the Decidua of Women with Recurrent Miscarriage and Normal Pregnancy. Placenta . (2004) 25: 140–5
  200. Tirado-Gonzalez I, Munoz-Fernandez R, Blanco O, Leno-Duran E, Abadia-Molina AC, Olivares EG. Reduced proportion of decidual DC-SIGN+ cells in human spontaneous abortion. Placenta. (2010) 31:1019–22.
  201. Giuliani E, Parkin KL, Lessey BA, Young SL, Fazleabas AT. Characterization of Uterine NK Cells in Women with Infertility or Recurrent Pregnancy Loss and Associated Endometriosis. Am J Reprod Immunol . (2014) 72: 262–69
  202. Clifford K, Flanagan AM, Regan L. Endometrial CD56+Natural Killer Cells in Women with Recurrent Miscarriage: A Histomorphometric Study.Hum Reprod. (1999) 14: 2727–30.
  203. Tuckerman E, Laird SM, Prakash A, Li TC. Prognostic Value of the Measurement of Uterine Natural Killer Cells in the Endometrium of Women with Recurrent Miscarriage. Hum Reprod. (2007) 22: 2208–13.
  204. Kuon RJ, Weber M, Heger J, Santillan I, Vomstein K, Bar C, Strowitzki T, Markert UR, Toth B. Uterine Natural Killer Cells in Patients with Idiopathic Recurrent Miscarriage. Am J Reprod Immunol. (2017) 78: e12721.
  205. El-Azzamy H, Dambaeva SV, Katukurundage D, Salazar Garcia MD, Skariah A, Hussein Y, Germain A, Fernandez E, Gilman-Sachs A, Beaman KD, et al. Dysregulated Uterine Natural Killer Cells and Vascular Remodeling in Women with Recurrent Pregnancy Losses. Am J Reprod Immunol.(2018) 80: e13024.
  206. Seshadri S, Sunkara SK. Natural Killer Cells in Female Infertility and Recurrent Miscarriage: A Systematic Review and Meta-Analysis.Hum Reprod Update . (2014) 20: 429–38.
  207. Kuon RJ, Vomstein K, Weber M, Muller F, Seitz C, Wallwiener S, Strowitzki T, Schleussner E, Markert UR, Daniel V, et al. The “Killer Cell Story” in Recurrent Miscarriage: Association Between Activated Peripheral Lymphocytes and Uterine Natural Killer Cells. J Reprod Immunol. (2017) 119: 9–14.
  208. Fuchinoue K, Fukui A, Chiba H, Kamoi M, Funamizu A, Taima A, Fukuhara R, Mizunuma H. Expression of Retinoid-Related Orphan Receptor (ROR)γt on NK22 Cells in the Peripheral Blood and Uterine Endometrium of Women with Unexplained Recurrent Pregnancy Loss and Unexplained Infertility.J Obstet Gynaecol Res . (2016) 42: 1541–52
  209. Kwak-Kim J, Yang KM, Gilman-Sachs A. Recurrent Pregnancy Loss: A Disease of Inflammation and Coagulation. J Obstet Gynaecol Res.(2009) 35: 609–22.
  210. O’Hern Perfetto C, Fan X, Dahl S, Krieg S, Westphal LM, Bunker Lathi R, Nayak NR. Expression of Interleukin-22 in Decidua of Patients with Early pregnancy and Unexplained Recurrent Pregnancy Loss. J Assist Reprod Genet. (2015) 32: 977–84.
  211. Schumacher A, Ehrentraut S, Scharm M, Wang H, Hartig R, Morse HC III, et al. Plasma cell alloantigen 1 and IL-10 secretion define two distinct peritoneal B1a B cell subsets with opposite functions, PC1(high) cells being protective and PC1(low) cells harmful for the growing fetus. Front Immunol.  (2018) 9:1045. doi: 10.3389/fimmu.2018.01045
  212. AlJameil N, Tabassum H, AlMayouf H, Alshenefy A, Almohizea MM, Ali MN. Identification of serum cytokines as markers in women with recurrent pregnancy loss or miscarriage using milliplex analysis. (2018).
  213. Wilczyński JR, Radwan P, Tchórzewski H, Banasik M. Immunotherapy of patients with recurrent spontaneous miscarriage and idiopathic infertility: does the immunization-dependent Th2 cytokine overbalance really matter?. Arch Immunol Ther Exper. (2012) 60(2):151-60.
  214. Ismail AM, Agban MN, Hasanein AS, Rayan AA, Abbas AM. Role of Th-1 cell cytokines, leukemia inhibitory factor and hoxA genes in women with recurrent pregnancy loss. Mid East Fertil Soc J. (2017) 22:300-4.
  215. Xu L, Qiu T, Wang Y, Chen Y, Cheng W. Expression of C-type lectin receptors and Toll-like receptors in decidua of patients with unexplained recurrent spontaneous abortion. Reprod Fertil Develop (2017) 29:1613-24.
  216. Comba C, Bastu E, Dural O, Yasa C, Keskin G, Ozsurmeli M, Buyru F, Serdaroglu H. Role of Inflammatory Mediators in Patients with Recurrent Pregnancy Loss. Fertil Steril. (2015) 104: 1467–74
  217. Jasper MJ, Tremellen KP, Robertson SA. Reduced Expression of IL-6 and IL-1alpha mRNAs in Secretory Phase Endometrium of Women with Recurrent Miscarriage. J Reprod Immunol. (2007) 73: 74–84.
  218. Von Wolff M, Thaler CJ, Strowitzki T, Broome J, Stolz W, Tabibzadeh S. Regulated Expression of Cytokines in Human Endometrium Throughout the Menstrual Cycle: Dysregulation in Habitual Abortion. Mol Hum Reprod. (2000) 6:627–34
  219. Krieg SA, Fan X, Hong Y, Sang QX, Giaccia A, Westphal LM, Lathi RB, Krieg AJ, Nayak NR. Global Alteration in Gene Expression Profiles of Deciduas from Women with Idiopathic Recurrent Pregnancy Loss.Mol Hum Reprod. (2012) 189: 442–50.
  220. Gao Y, Wang P, Zou T, Zhang Z, Liang W. Increased Th17 and reduced Treg cells in patients with unexplained recurrent spontaneous abortion. Clin Experim Obstet Gynecol. (2019) 46:458-60.
  221. Monastero RN, Pentyala S. Cytokines as biomarkers and their respective clinical cutoff levels. Int J Inflammat. (2017) 2017.
  222. Liang PY, Diao LH, Huang CY, Lian RC, Chen X, Li GG, Zhao J, Li YY, He XB, Zeng Y. The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure. Reprod Bomed online. (2015) 31:823-6.
  223. Salama KM, Alloush MK. Are the cytokines TNF alpha and IL 1Beta early predictors of embryo implantation? Cross sectional study. J Reprod Immunol. (2020) 137:102618
  224. Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Llurba E, Gris JM. Tumor necrosis factor-alpha and pregnancy: focus on biologics. An updated and comprehensive review. Clin Rev Allergy Immunol . (2017) 53:40-53.
  225. Ruiz-Alonso M, Blesa D, Simon C. The genomics of the human endometrium. Biochim Biophys Acta. (2012) 1822:1931-42.
  226. Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol. (2017)17:469-82.
  227. Kosova G, Stephenson MD, Lynch VJ, Ober C. Evolutionary forward genomics reveals novel insights into the genes and pathways dysregulated in recurrent early pregnancy loss. Hum Reprod.(2015) 30:519-29.
  228. Beydoun H, Saftlas AF. Association of human leucocyte antigen sharing with recurrent spontaneous abortions. Tiss Antig. (2005) 65:123–35.
  229. Chau A, Markley JC, Juang J, Tsen LC. Cytokines in the perinatal period–Part I. Int J Obstet Anesth. (2016) 26: 39-47.
  230. Cartwright JE, Fraser R, Leslie K, Wallace AE, James JL. Remodelling at the maternal–fetal interface: relevance to human pregnancy disorders. Reprod. (2010) 140:803-13.
  231. Lyzikova YA, Zinovkin DA, Pranjol MZ. Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with recurrent miscarriages. Europ J Obstet Gynecol Reprod Biol. (2020) 245:121-6.
  232. Tabibzadeh S, Sun XZ. Cytokine expression in human endometrium throughout the menstrual cycle. Hum Reprod. (1992) 7:1214-21.
  233. Linjawi S, Li TC, Tuckerman EM, Blakemore AI, Laird SM. Expression of interleukin-11 receptor α and interleukin-11 protein in the endometrium of normal fertile women and women with recurrent miscarriage. J Reprod Immunol. (2004) 64:145-55.
  234. Yui J, Garcia-Lloret M, Wegmann TG, Guilbert LJ. Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. Placent. (1994) 15:819-35.
  235. Haddad EK, Duclos AJ, Antecka E, Lapp WS, Baines MG. Role of interferon-gamma in the priming of decidual macrophages for nitric oxide production and early pregnancy loss. Cell Immunol. (1997) 181:68-75.
  236. Knofler M, Mosl B, Bauer S, Griesinger G, Husslein P.TNF-alpha/TNFRI in primary and immortalized first trimester cytotrophoblasts.Placent. (2000) 21:525-35.
  237. Jokhi PP, King A, Boocock C, Loke YW. Secretion of colony stimulating factor-1 by human first trimester placental and decidual cell populations and the effect of this cytokine on trophoblast thymidine uptake invitro. Hum Reprod . (1995) 10:2800-7.
  238. Hamilton GS, Lysiak JJ, Watson AJ, Lala PK. Effects of colony stimulating factor-1 on human extravillous trophoblast growth and invasion. J Endocrinol. (1998) 159: 69-77.
  239. Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Köntgen F, Abbondanzo SJ. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nat. (1992) 359:76.
  240. Piccinni MP. T cells in normal pregnancy and recurrent pregnancy loss.Reprod BioMed Online. (2006) 13:840-4.
  241. Bennett WA, Lagoo-Deenadayalan S, Whitworth NS, Stopple JA, Barber, WH, Hale E, et al. First trimester human, inflammatory cvebia, the carfiir, cytokine network of pregnancy. Am J Reprod Immunol . (1999) 41:70-78.
  242. Bennett W, Lagoo-Deenadayalan S, Whitworth N, Brackin M, Hale E, Cowan B. Expression and production of interleukin-10 by human trophoblast: relationship to pregnancy immunotolerance. Biol Med: Official J Societ Invest Early Pregn. (1997) 3:190-8.
  243. Hakimi H, Zare-Bidaki M, Zainodini N, Assar S, Arababadi MK. Significant roles played by IL-10 in chlamydia infections.Inflammat. (2014) 37: 818-23.
  244. Robertson SA, Skinner RJ, Care AS. Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice.J Immunol. (2006) 177:4888-96.
  245. Zhang A, Fu J, Ning B, Li D, Sun N, Wei W, et al. Tolerogenic dendritic cells generated with IL10/TGFβ1 relieve immune thrombocytopenia in mice. Thromb Res. (2013) 132 :63-68.
  246. Teng CB, Diao HL, Ma H, Cong J, Yu H, Ma XH, et al. Signal transducer and activator of transcription 3 (Stat3) expression and activation in rat uterus during early pregnancy. Reprod. (2004) 128:197-205.
  247. Ladyman SR, Grattan DR. Region-specific reduction in leptin-induced phosphorylation of signal transducer and activator of transcription-3 (STAT3) in the rat hypothalamus is associated with leptin resistance during pregnancy. Endocrinol. (2004) 145: 3704-11.
  248. Hutchins AP, Diez D, Miranda-Saavedra D. The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges.Brief Funct Genom. (2013) 12 :489-98.
  249. Liu B, Wu H, Huang Q, Li M, Fu X. Phosphorylated STAT3 inhibited the proliferation and suppression of decidual Treg cells in unexplained recurrent spontaneous abortion. Int Immunopharmacol. (2020) 82:106337.
  250. Thaxton JE, Sharma S. Interleukin‐10: a multi‐faceted agent of pregnancy. Am J Reprod Immunol. (2010) 63:482-91.
  251. Chaouat G, Meliani AA, Martal J, Raghupathy R, Elliott JF, Elliot J, Mosmann T, Wegmann TG. IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-tau. J Immunol. (1995) 154 :4261-8.
  252. Tabibzadeh S. Ubiquitous expression of TNFα/cachectin in human endometrium. Am J Reprod Immunol. ( 1991) 26:1-4.
  253. Hunt JS, Chen HL, Hu XL, Tabibzadeh S. Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium. Hum Reprod. (1992) 47: 141-7.
  254. Philippeaux MM, Piguet PF. Expression of tumour necrosis factor-alpha and its mRNA in the endometrial mucosa during the menstrual cycle.Am J Pathol. (1993) 143:480-6.
  255. Haimovici F, Hill JA, Anderson DJ. The effects of soluble products of activated lymphocytes and macrophages on blastocyts implantation events in vitro. Biol Reprod. (1991) 44:69-75.
  256. Suffys P, Beyaert R, Van RF, Fiers W. TNF in combination with interferon-gamma is cytotoxic to normal, untransformed mouse and rat embryo fibroblast-like cells. Antican Res. ( 1989) 9:167-71.
  257. Mueller-Eckhardt G, Mallmann P, Neppert J, Lattermann A, Melk A, Heine O, Pfeiffer R, Zingsem J, Domke N, Mohr-Pennert A. Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. J Reprod Immunol . (1994) 27: 95-109.
  258. Jenkins C, Roberts J, Wilson R, Mac Lean MA, Shilito J, Walker JJ. Evidence of a TH1 type response associated with recurrent miscarriage.Fertil Steril. (2000) 6:1206-8.
  259. Trincheiri G. Interleukin-12 and its role in the generation of Th-1 cells. Immunol Today. (1993) 14:335-8.
  260. Hill JA, Polgar K, Anderson DJ. T-helper1-type immunity totrophoblast in women with recurrent spontaneous abortion. JAMA. (1995) 273:1933-6.
  261. Michimata T, Tsuda H, Sakai M, Fujimura M, Nagata K, Nakamura M, Saito S. Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner. Mol Hum Reprod. (2002) 8: 181-7.
  262. Michimata T, Sakai M, Miyazaki S, Ogasawara MS, Suzumori K, Aoki K, Nagata K, Saito S. Decrease of T‐helper 2 and T‐cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content. Hum Reprod . (2003) 18:1523-8.
  263. Krishnan L, Guilbert LJ, Wegmann TG, Belosevic M, Mosmann TR.T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells.J Immunol. (1996) 156:653-62.
  264. Daher S, Fonseca F, Ribeiro OG, Musatti CC, Gerbase-DeLima M. Tumor necrosis factor during pregnancy and the onset of labor and spontaneous abortion. Eur J Obstet Gynecol Reprod Biol. (1999) 83:77-9.
  265. Hehlgans T, Pfeffer K. The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunol . (2005) 115:1-20.
  266. Kwak-Kim JY, Gilman-Sachs A, Kim CE. T helper 1 and 2 immune responses in relationship to pregnancy, nonpregnancy, recurrent spontaneous abortions and infertility of repeated implantation failures.Chem Immunol Aller. (2005) 88:64-79.
  267. Garcia-Lloret MI, Winkler-Lowen B, Guilbert LJ. Monocytes adhering by LFA-1 to placental syncytiotrophoblasts induce local apoptosis via release of TNF-α. A model for hematogenous initiation of placental inflammations. J Leukocyt Biol. (2000) 68:903-8.
  268. Fortunato SJ, Menon R, Lombardi SJ. Support for an infection induced apoptotic pathway in human fetal membranes. Am J Obstet Gynecol. (2001) 184:1392-8.
  269. Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. (2000) 15:713-8.
  270. Kinsky R, Delage G, Rosin N, Thang MN, Hoffmann M, Chaouat G.A murine model of NK cell mediated resorption. Am J Reprod Immunol.(1990) 23:73-7.
  271. Paganin C, Matteucci C, Cenzuales S, Mantovani A, Allavena P. IL-4inhibits binding and cytotoxicity of NK cells to vascular endothelium. Cytokine. (1994) 6:135-40.
  272. Loza MJ, Peters SP, Zangrilli JG, Perussia B. Distinction between IL-13+ and IFN-γ+ natural killer cells and regulation of their pool size by IL-4. Eur J Immunol. (2002) 32:413-23.
  273. Seo N, Tokura Y, Furukawa F, Takigawa M. Down-regulation of tumoricidal NK and NK T cell activities by MHC Kb molecules expressed on Th2-type γ δ T and αβ T cells coinfiltrating in early B16 melanoma lesions. J Immunol. (1998) 161:4138-45.
  274. Deniz G, Akdis M, Aktas E, Blaser K, Akdis CA. Human NK1 and NK2 subsets determined by purification of IFN-γ-secreting and IFN-γ-nonsecreting NK cells. Eur J Immunol. ( 2002) 32:879-84.
  275. 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
  276. Zhang J, Chen Z, Smith GN, Croy BA. Natural Killer Cell-Triggered Vascular Transformation: Maternal Care Before Birth? Cell Mol Immunol. (2011) 8: 1–11
  277. Helige C, Ahammer H, Moser G, Hammer A, Dohr G, Huppertz B, Sedlmayr P. Distribution of Decidual Natural Killer Cells and Macrophages in the Neighbourhood of the Trophoblast Invasion Front: A Quantitative Evaluation. Hum Reprod. (2014) 29: 8–17.
  278. Koopman LA, Kopcow HD, Rybalov B, Boyson JE, Orange JS, Schatz F, Masch R, Lockwood CJ, Schachter AD, Park PJ, et al. Human Decidual Natural Killer Cells are a Unique NK Cell Subset with Immunomodulatory Potential. J Exp Med . (2003) 198: 1201–12.
  279. Liu S, Diao L, Huang C, Li Y, Zeng Y, Kwak-Kim JYH. The Role of Decidual Immune Cells on Human Pregnancy. J Reprod Immunol.(2017) 124:44–53.
  280. Moffett A, Chazara O, Colucci F. Maternal Allo-Recognition of the Fetus. Fertil Steril. (2017) 107: 1269–72.
  281. Kennedy PR, Chazara O, Gardner L, Ivarsson MA, Farrell LE, Xiong S, Hiby SE, Colucci F, Sharkey AM, Moffett, A. Activating KIR2DS4 Is Expressed by Uterine NK Cells and Contributes to Successful Pregnancy.J Immunol. (2016) 197: 4292–4300
  282. Sharkey AM, Xiong S, Kennedy PR, Gardner L, Farrell LE, Chazara O, Ivarsson MA, Hiby SE, Colucci F, Moffett A. Tissue-Specific Education of Decidual NK Cells. J Immunol. (2015) 195: 3026–32.
  283. Moffett A. NK Cell Allorecognition. Nat Rev Immunol. (2017) 17:466.
  284. Penman BS, Moffett A, Chazara O, Gupta S, Parham P. Reproduction, Infection and Killer-Cell Immunoglobulin-Like Receptor Haplotype Evolution. Immunogenet. (2016) 68: 755–64
  285. Brighton PJ, Maruyama Y, Fishwick K, Vrljicak P, Tewary S, Fujihara R, Muter J, Lucas ES, Yamada T, Woods L, Lucciola R. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Elife. (2017) 6:e31274.
  286. Somigliana E, Vigano P, Vignali M. Endometriosis and unexplained recurrent spontaneous abortion: pathological states resulting from aberrant modulation of natural killer function? Hum Reprod Update . (1999) 5:40-51.
  287. Kim SG, Paek MY, Ko IG. Peripheral blood level of natural killer cells in pregnant women with recurrent spontaneous abortion during the 6–12 weeks gestation. Arch Med Heal Sc. (2019) 7:191.
  288. Zhang YN, Huang CY, Lian RC, Xu J, Fu YF, Zeng Y, Tu WW. Relationship between the cytotoxic activity of peripheral blood natural killer cells and recurrent miscarriage. (2020).
  289. Sokolov DI, Mikhailova VA, Agnayeva AO, Bazhenov DO, Khokhlova EV, Bespalova ON, Gzgzyan AM, Selkov SA. NK and trophoblast cells interaction: cytotoxic activity on recurrent pregnancy loss.Gynecol Endocrinol. (2019) 35(sup1):5-10.
  290. Chaouat G. Regulation of T-cell activities at the feto-placental interface by placenta? Am J Reprod Immunol. (1999) 42:199-204.
  291. Dealtry GB, Clark DE, Sharkey A, Charnock-Jones DS, Smith SK. VII international congress of reproductive immunology. New Delhi, 27–30 October 1998: expression and localization of the Th2-type cytokine interleukin-13 and its receptor in the placenta during human pregnancy. Am J Reprod Immunol. (1998) 40:283-90.
  292. Roth I, Corry DB, Locksley RM, Abrams JS, Litton MJ, Fisher SJ. Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10. J Exper Med . (1996)184:539-48.
  293. Jones CA, Finlay-Jones JJ, Hart PH. Type-1 and type-2 cytokines in human late-gestation decidual tissue. Bio Reprod. (1997) 57:303-11.
  294. Bennett WA, Lagoo-Deenadayalan S, Brackin MN, Hale E, Cowan BD. Cytokine expression by models of human trophoblast as assessed by a semiquantitative reverse transcription-polymerase chain reaction technique. Am J Reprod Immunol .(1996) 36:285-94.
  295. Lim KJ, Odukoya OA, Ajjan RA, Li TC, Weetman AP, Cooke ID. Profile of cytokine mRNA expression in peri-implantation human endometrium.Mol Hum Reprod. (1998) 4:77-81.
  296. Saito S. Cytokine network at the feto-maternal interface. J Reprod Immunol. (2000) 47:87-103.
  297. Vives A, Balasch J, Yague J, Quinto L, Ordi J, Vanrell JA. Type-1 and type-2 cytokines in human decidual tissue and trophoblasts from normal and abnormal pregnancies detected by reverse transcriptase polymerase chain reaction (RT-PCR). Am J Reprod Immunol. (1999) 42:361-8.
  298. Lea RG, Tulppala M, Critchley HO. Deficient syncytiotrophoblast tumour necrosis factor-alpha characterizes failing first trimester pregnancies in a sub-group of recurrent miscarriage patients. Hum Reprod.(1997) 12:1313-20.
  299. Ledee-Bataille N, Dubanchet S, Coulomb-Lhermine A, Durand-Gasselin I,Frydman R, Chaouat G. A new role for natural killer cells, interleukin (IL)-12 and IL-18 in repeated implantation failure after invitro fertilization. Fertil Steril. (2004) 81:59-65.
  300. Jasper MJ, Tremellen KP, Robertson SA. Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod. (2006) 12:301-8.
  301. Hu X, Wang Y, Mor G, Liao A. Forkhead box P3 is selectively expressed in human trophoblasts and decreased in recurrent pregnancy loss.Placenta. (2019) 81:1-8.
  302. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. (2005) 6:345-52.
  303. Akbar AN, Vukmanovic-Stejic M, Taams LS, Macallan DC. The dynamic co-evolution of memory and regulatory CD4+ T cells in the periphery.Nat Rev Immunol. (2007) 7:231-7.
  304. Shevach EM. Mechanisms of Foxp3+ T regulatory cell mediated suppression. Immunity. (2009) 30:636-45.
  305. Salker MS, Nautiyal J, Steel JH, Webster Z, Šućurović S, Nicou M, Singh Y, Lucas ES, Murakami K, Chan YW, James S. Disordered IL-33/ST2 activation in decidualizing stromal cells prolongs uterine receptivity in women with recurrent pregnancy loss. PLoSone. (2012) 7:1-18.
  306. Salker M, Teklenburg G, Molokhia M, Lavery S, Trew G, Aojanepong T, Mardon HJ, Lokugamage AU, Rai R, Landles C, Roelen BA. Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PloS one . (2010) 5:1-7.
  307. Tan SY, Hang F, Purvarshi G, Li MQ, Meng DH, Huang LL. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.Taiw J Obstet Gynecol. (2015) 54:522-6.
  308. Lockwood CJ, Huang SJ, Chen CP, Huang Y, Xu J, Faramarzi S, Kayisli O, Kayisli U, Koopman L, Smedts D, Buchwalder LF. Decidual Cell Regulation of Natural Killer Cell–Recruiting Chemokines: Implications for the Pathogenesis and Prediction of Preeclampsia. Am J Pathol. (2013) 183:841-56.
  309. Li A, Dubey S, Varney ML, Dave BJ, Singh RK. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol. (2003) 170:3369-76.
  310. Tsuda S, Nakashima A, Shima T, Saito S. New paradigm in the role of regulatory T cells during pregnancy. Front Immunol. (2019) 10:573.
  311. Schjenken JE, Moldenhauer LM, Zhang B, Care AS, Groome HM, Chan HY, Hope CM, Barry SC, Robertson SA. MicroRNA miR-155 is required for expansion of regulatory T cells to mediate robust pregnancy tolerance in mice. Mucosal Immunol. (2020):1-7.
Figure Legends
Fig 1 The different types of decidua (decidua parietalis, capsularis and basalis) and the intimate association between the developing embryo and the placental tissue. Decidua basalis develops from the endometrium that immediately lies under the site of implantation while as decidua capsularis originate from the thin endometrial stroma rim that covers the blastocyst. The endometrium that lines remaining part of uterine cavity forms decidua parietalis. Decidua provides nutrition to the growing embryo before the formation of placenta and more importantly plays a key role in shielding embryo from the maternal immune cell attack
Fig 2 Micrographic representation of stromal decidual cells. These cells are large polygonal with nuclei that stain pale and possess eosinophilic granular cytoplasm
Fig 3 A preparatory pathway for embryo implantation and pregnancy. Decidualization that begins during the menstrual cycle (midsecretory phase) in response to increased estrogen and progesterone levels involves the transformation of endometrial stromal cells into decidual cells in inflammatory and anti-inflammatory milieu via retinoid and corticosteroid signaling pathway reprogramming as well as regulates the specific uNK cells (CD56 bright and CD16 dim) that in turn control inflammation, angiogenesis and vascular remodeling via IL15 and IL11. The inflammatory responses synchronize the implantation window. IL11 is stimulated by relaxin and PGE2 via cAMP/PKA signaling pathway whereas prokineticin-1 triggers it via calcineurin-NFAT signaling pathway and this cytokine is linked with decidualization, implantation and placentation.
Table 1 Overview of cytokines with their nature and cellular source