Genetic regulation of recurrent spontaneous abortion in humans

Biomedical Journal

Volumn 38, Issue 1, 2015, Pages 11-24

  Vaiman, Daniel ^a  

^a INSTITUT COCHIN   (France)

Author keywords

genetics; infertility; recurrent miscarriage

Indexed keywords

FREE RADICAL; CYTOKINE;

AUTOIMMUNE DISEASE; DNA POLYMORPHISM; ETHNIC GROUP; FERTILIZATION; FETOPLACENTAL UNIT; GENETIC ANALYSIS; GENETIC REGULATION; GENETIC VARIABILITY; GESTATIONAL AGE; HUMAN; IMMUNOPATHOLOGY; MALE INFERTILITY; NIDATION; NONHUMAN; PLOIDY; PREGNANCY DISORDER; RECURRENT ABORTION; REVIEW; SPONTANEOUS ABORTION; THROMBOPHILIA; FEMALE; GENETICS; HUMAN CHROMOSOME; IMMUNOLOGY; METABOLISM; PREGNANCY; SOLUTIO PLACENTAE; UTERUS;

ABORTION, HABITUAL; ABRUPTIO PLACENTAE; CHROMOSOMES, HUMAN; CYTOKINES; FEMALE; HUMANS; PREGNANCY; THROMBOPHILIA; UTERUS;

EID: 84923375493     PISSN: 23194170     EISSN: None     Source Type: Journal    
DOI: 10.4103/2319-4170.133777     Document Type: Review

References (145)

1. Kalousek DK. The effect of confined placental mosaicism on development of the human aneuploid conceptus. Birth Defects Orig Artic Ser 1993;29:39-51
2. Liu J, Wang W, Sun X, Liu L, Jin H, Li M, et al. DNA microarray reveals that high proportions of human blastocysts from women of advanced maternal age are aneuploid and mosaic. Biol Reprod 2012;87:148
3. Robinson WP, McFadden DE, Stephenson MD. The origin of abnormalities in recurrent aneuploidy/polyploidy. Am J Hum Genet 2001;69:1245-54
4. Kurahashi H, Kogo H, Tsutsumi M, Inagaki H, Ohye T. Failure of homologous synapsis and sex-specific reproduction problems. Front Genet 2012;3:112
5. Musacchio A, Salmon ED. The spindle-Assembly checkpoint in space and time. Nat Rev Mol Cell Biol 2007;8:379-93
6. Lopez-Carrasco A, Oltra S, Monfort S, Mayo S, Rosello M, Martinez F, et al. Mutation screening of AURKB and SYCP3 in patients with reproductive problems. Mol Hum Reprod 2013;19:102-8
7. Shi Q, Hu M, Luo M, Liu Q, Jiang F, Zhang Y, et al. Reduced expression of Mad2 and Bub1 proteins is associated with spontaneous miscarriages. Mol Hum Reprod 2011;17:14-21
8. Nath S, Moghe M, Chowdhury A, Godbole K, Godbole G, Doiphode M, et al. Is germline transmission of MAD2 gene deletion associated with human fetal loss? Mol Hum Reprod 2012;18:554-62
9. Caburet S, Arboleda VA, Llano E, Overbeek PA, Barbero JL, Oka K, et al. Mutant cohesin in premature ovarian failure. N Engl J Med 2014;370:943-9
10. Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, et al. The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood 2012;120:5063-72
11. Lyu SW, Song H, Yoon JA, Chin MU, Sung SR, Kim YS, et al. Transcriptional profiling with a pathway-oriented analysis in the placental villi of unexplained miscarriage. Placenta 2013;34:133-40
12. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 2007;447:1087-93
13. Kirkinezos IG, Moraes CT Reactive oxygen species and mitochondrial diseases. Semin Cell Dev Biol 2001;12:449-57
14. Gupta S, Agarwal A, Banerjee J, Alvarez JG. The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: A systematic review. Obstet Gynecol Surv 2007;62:335-47
15. Ruder EH, Hartman TJ, Goldman MB. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol 2009;21:219-22
16. Khadzhieva MB, Lutcenko NN, Volodin IV, Morozova KV, Salnikova LE. Association of oxidative stress-related genes with idiopathic recurrent miscarriage. Free Radic Res 2014;48:534-41
17. Tarry-Adkins JL, Martin-Gronert MS, Fernandez-Twinn DS, Hargreaves I, Alfaradhi MZ, Land JM, et al. Poor maternal nutrition followed by accelerated postnatal growth leads to alterations in DNA damage and repair, oxidative and nitrosative stress, and oxidative defense capacity in rat heart. FASEB J 2013;27:379-90
18. Cotechini T, Komisarenko M, Sperou A, Macdonald-Goodfellow S, Adams MA, Graham CH. Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J Exp Med 2014;211:165-79
19. Myatt L. Review: Reactive oxygen and nitrogen species and functional adaptation of the placenta. Placenta 2010;31 Suppl: S66-9
20. Su MT, Lin SH, Chen YC. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: A systematic review and meta-Analysis. Hum Reprod Update 2011;17:803-12
21. Tempfer C, Unfried G, Zeillinger R, Hefler L, Nagele F, Huber JC. Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage. Hum Reprod 2001;16:1644-7
22. Suryanarayana V, Rao L, Kanakavalli M, Padmalatha V, Deenadayal M, Singh L. Recurrent early pregnancy loss and endothelial nitric oxide synthase gene polymorphisms. Arch Gynecol Obstet 2006;274:119-24
23. Fan W, Li SW, Wang Y. Association of genetic polymorphisms in endothelial nitric oxide synthase 3 gene with recurrent early spontaneous abortion. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2007;24:23-6
24. Shin SJ, Lee HH, Cha SH, Kim JH, Shim SH, Choi DH, et al. Endothelial nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) and haplotypes in Korean patients with recurrent spontaneous abortion. Eur J Obstet Gynecol Reprod Biol 2010;152:64-7
25. Parveen F, Faridi RM, Das V, Tripathi G, Agrawal S. Genetic association of phase I and phase II detoxification genes with recurrent miscarriages among North Indian women. Mol Hum Reprod 2009;16:207-14
26. Hefler LA, Tempfer CB, Bashford MT, Unfried G, Zeillinger R, Schneeberger C, et al. Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1beta gene promoter in women with idiopathic recurrent miscarriage. Mol Hum Reprod 2002;8:95-100
27. Buchholz T, Lohse P, Kosian E, Thaler CJ. Vasoconstrictively acting AT1R A1166C and NOS3 4/5 polymorphisms in recurrent spontaneous abortions (RSA). Am J Reprod Immunol 2004;51:323-8
28. Makino A, Nakanishi T, Sugiura-Ogasawara M, Ozaki Y, Suzumori N, Suzumori K. No association of C677T methylenetetrahydrofolate reductase and an endothelial nitric oxide synthase polymorphism with recurrent pregnancy loss. Am J Reprod Immunol 2004;52:60-6
29. Zammiti W, Mtiraoui N, Mahjoub T. Lack of consistent association between endothelial nitric oxide synthase gene polymorphisms, homocysteine levels and recurrent pregnancy loss in tunisian women. Am J Reprod Immunol 2008;59:139-45
30. Karvela M, Papadopoulou S, Tsaliki E, Konstantakou E, Hatzaki A, Florentin-Arar L, et al. Endothelial nitric oxide synthase gene polymorphisms in recurrent spontaneous abortions. Arch Gynecol Obstet 2008;278:349-52
31. Munafo MR, Flint J. Meta-Analysis of genetic association studies. Trends Genet 2004;20:439-44
32. Bonney EA, Matzinger P. The maternal immune system's interaction with circulating fetal cells. J Immunol 1997;158:40-7
33. Chaouat G. Inflammation, NK cells and implantation: Friend and foe (the good, the bad and the ugly?): Replacing placental viviparity in an evolutionary perspective. J Reprod Immunol 2013;97:2-13
34. Gill TJ 3rd. Role of the major histocompatibility complex region in reproduction, cancer, and autoimmunity. Am J Reprod Immunol 1996;35:211-5
35. Coulam CB, Kaider BD, Kaider AS, Janowicz P, Roussev RG. Antiphospholipid antibodies associated with implantation failure after IVF/ET. J Assist Reprod Genet 1997;14:603-8
36. Carp HJ, Selmi C, Shoenfeld Y. The autoimmune bases of infertility and pregnancy loss. J Autoimmun 2012;38:J266-274
37. Shoenfeld Y, Carp HJ, Molina V, Blank M, Cervera R, Balasch J, et al. Autoantibodies and prediction of reproductive failure. Am J Reprod Immunol 2006;56:337-44
38. Moravej A, Jeddi-Tehrani M, Salek-Moghaddam AR, Dokouhaki P, Ghods R, Rabbani H, et al. Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy. Am J Reprod Immunol 2010;64:97-103
39. Salmon JE, Heuser C, Triebwasser M, Liszewski MK, Kavanagh D, Roumenina L, et al. Mutations in complement regulatory proteins predispose to preeclampsia: A genetic analysis of the PROMISSE cohort. PLoS Med 2011;8:e1001013
40. Girardi G, Yarilin D, Thurman JM, Holers VM, Salmon JE. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 2006;203:2165-75
41. Galazios G, Papazoglou D, Tsikouras P, Kolios G. Vascular endothelial growth factor gene polymorphisms and pregnancy. J Matern Fetal Neonatal Med 2009;22:371-8
42. Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, Mercier E, Fabbro-Peray P, Balducchi JP, et al. Comparative incidence of pregnancy outcomes in thrombophilia-positive women from the NOH-APS observational study. Blood 2014;123:414-21
43. Fang CJ, Fremeaux-Bacchi V, Liszewski MK, Pianetti G, Noris M, Goodship TH, et al. Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood 2008;111:624-32
44. Risk JM, Flanagan BF, Johnson PM. Polymorphism of the human CD46 gene in normal individuals and in recurrent spontaneous abortion. Hum Immunol 1991;30:162-7
45. Laitinen T, Lokki ML, Tulppala M, Ylikorkala O, Koskimies S. Tumour necrosis factor B gene polymorphism in relation to complotype in couples with spontaneous abortions and in control families. Scand J Immunol 1992;35:131-5
46. Zutshi N, Gandhi M, Kaul P. CD46 polymorphism: A probable risk factor for recurrent spontaneous abortion in a northern Indian population. Natl Med J India 2010;23:85-7
47. Mohlin FC, Mercier E, Fremeaux-Bacchi V, Liszewski MK, Atkinson JP, Gris JC, et al. Analysis of genes coding for CD46, CD55, and C4b-binding protein in patients with idiopathic, recurrent, spontaneous pregnancy loss. Eur J Immunol 2013;43:1617-29
48. Dausset J. The major histocompatibility complex in man. Science 1981;213:1469-74
49. Faulk WP, Sanderson AR, Temple A. Distribution of MHC antigens in human placental chorionic villi. Transplant Proc 1977;9:1379-84
50. Hunt JS, Orr HT. HLA and maternal-fetal recognition. FASEB J 1992;6:2344-8
51. Redman CW, Bodmer JG, Bodmer WF, Beilin LJ, Bonnar J. HLA antigens in severe pre-eclampsia. Lancet 1978;2:397-9
52. Takakuwa K, Higashino M, Ueda H, Yamada K, Asano K, Yasuda M, et al. Significant compatibility does not exist at the HLA-DQB gene locus in couples with unexplained recurrent abortions. Am J Reprod Immunol 1992;28:12-6
53. Hataya I, Takakuwa K, Tanaka K. Human leukocyte antigen class II genotype in patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody. Fertil Steril 1998;70:919-23
54. Takakuwa K, Hataya I, Arakawa M, Kikuchi A, Higashino M, Yasuda M, et al. Possible susceptibility of the HLA-DPB1. 0402 and HLA-DPB1. 04 alleles to unexplained recurrent abortion: Analysis by means of polymerase chain reaction-restricted fragment length polymorphism method. Am J Reprod Immunol 1999;42:233-9
55. Takakuwa K, Adachi H, Hataya I, Ishii K, Tamura M, Tanaka K. Molecular genetic studies of HLA-DRB1 alleles in patients with unexplained recurrent abortion in the Japanese population. Hum Reprod 2003;18:728-33
56. Sagot P, Bignon J, Cesbron A, Cheneau ML, Boog G, Muller JY. Lack of evidence for a role of HLA-DP in unexplained recurrent spontaneous abortion. Transfus Clin Biol 1995;2:145-50
57. Christiansen OB, Mathiesen O, Husth M, Jersild C, Grunnet N. Studies of RFLP-inferred HLA-DR-DQ haplotypes in Danish women with recurrent fetal losses. Tissue Antigens 1992;40:134-9
58. Christiansen OB, Rasmussen KL, Jersild C, Grunnet N. HLA class II alleles confer susceptibility to recurrent fetal losses in Danish women. Tissue Antigens 1994;44:225-33
59. Kruse C, Steffensen R, Varming K, Christiansen OB. A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1.03 is associated with recurrent miscarriage. Hum Reprod 2004;19:1215-21
60. Laitinen T, Koskimies S, Westman P. Foeto-maternal compatibility in HLA-DR, -DQ, and -DP loci in Finnish couples suffering from recurrent spontaneous abortions. Eur J Immunogenet 1993;20:249-58
61. Lin Q, Lu P, Wang X. Study on human leucocyte antigen-DQ region gene polymorphism in cases of habitual abortion with anticardiolipin antibody. Zhonghua Fu Chan Ke Za Zhi 2000;35:208-11
62. Wang XP, Lin QD, Lu PH, Ma ZW, Zhao AM. Association of HLA-DQB1 coding region with unexplained recurrent spontaneous abortion. Chin Med J (Engl) 2004;117:492-7
63. Zheng ML, Niu LY. Association of soluble human leukocyte antigen DQB1 with recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi 2006;41:152-4
64. Bompeixe EP, Carvalho Santos PS, Vargas RG, von Linsingen R, Zeck SC, Wowk PF, et al. HLA class II polymorphisms and recurrent spontaneous abortion in a Southern Brazilian cohort. Int J Immunogenet 2012;40:186-91
65. Gonzalez A, Rebmann V, LeMaoult J, Horn PA, Carosella ED, Alegre E. The immunosuppressive molecule HLA-G and its clinical implications. Crit Rev Clin Lab Sci 2012;49:63-84
66. Hsu P, Santner-Nanan B, Dahlstrom JE, Fadia M, Chandra A, Peek M, et al. Altered decidual DC-SIGN+antigen-presenting cells and impaired regulatory T-cell induction in preeclampsia. Am J Pathol 2012;181:2149-60
67. Nowak I, Malinowski A, Tchorzewski H, Barcz E, Wilczynski JR, Banasik M, et al. HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion. J Reprod Immunol 2012;88:32-7
68. Hiby SE, Walker JJ, O'shaughnessy KM, Redman CW, Carrington M, Trowsdale J, et al. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 2004;200:957-65
69. Kotze D, Kruger TF. HLA-G as a marker for embryo selection in assisted reproductive technology. Fertil Steril 2013;100:e44
70. Karhukorpi J, Laitinen T, Tiilikainen AS. HLA-G polymorphism in Finnish couples with recurrent spontaneous miscarriage. Br J Obstet Gynaecol 1997;104:1212-4
71. Yamashita T, Fujii T, Tokunaga K, Tadokoro K, Hamai Y, Miki A, et al. Analysis of human leukocyte antigen-G polymorphism including intron 4 in Japanese couples with habitual abortion. Am J Reprod Immunol 1999;41:159-63
72. Hviid TV, Christiansen OB, Johansen JK, Hviid UR, Lundegaard C, Moller C, et al. Characterization of a new HLA-G allele encoding a nonconservative amino acid substitution in the alpha3 domain (exon 4) and its relevance to certain complications in pregnancy. Immunogenetics 2001;53:48-53
73. Aldrich CL, Stephenson MD, Karrison T, Odem RR, Branch DW, Scott JR, et al. HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Mol Hum Reprod 2001;7:1167-72
74. Hviid TV, Hylenius S, Hoegh AM, Kruse C, Christiansen OB. HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens 2002;60:122-32
75. Hviid TV, Hylenius S, Lindhard A, Christiansen OB. Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome. Tissue Antigens 2004;64:66-9
76. Tripathi P, Abbas A, Naik S, Agrawal S. Role of 14-bp deletion in the HLA-G gene in the maintenance of pregnancy. Tissue Antigens 2004;64:706-10
77. Kano T, Mori T, Furudono M, Ishikawa H, Watanabe H, Kikkawa E, et al. Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy. Am J Reprod Immunol 2007;58:383-7
78. Yan WH, Fan LA, Yang JQ, Xu LD, Ge Y, Yao FJ. HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion. Int J Immunogenet 2006;33:55-8
79. Yan WH, Lin A, Chen XJ, Dai MZ, Gan LH, Zhou MY, et al. Association of the maternal 14-bp insertion polymorphism in the HLA-G gene in women with recurrent spontaneous abortions. Tissue Antigens 2006;68:521-3
80. Sipak-Szmigiel O, Cybulski C, Lubinski J, Ronin-Walknowska E. HLA-G polymorphism in a Polish population and reproductive failure. Tissue Antigens 2008;71:67-71
81. Sipak-Szmigiel O, Cybulski C, Wokolorczyk D, Lubinski J, Kurzawa R, Baczkowski T, et al. HLA-G polymorphism and in vitro fertilization failure in a Polish population. Tissue Antigens 2009;73:348-52
82. Aruna M, Sirisha PV, Andal Bhaskar S, Tarakeswari S, Thangaraj K, Reddy BM. Role of 14-bp insertion/deletion polymorphism in HLA-G among Indian women with recurrent spontaneous abortions. Tissue Antigens 2011;77:131-5
83. Jassem RM, Shani WS, Loisel DA, Sharief M, Billstrand C, Ober C. HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq. Hum Immunol 2012;73:811-7
84. Xue S, Yang J, Yao F, Xu L, Fan L. Recurrent spontaneous abortions patients have more -14 bp/+14 bp heterozygotes in the 3UT region of the HLA-G gene in a Chinese Han population. Tissue Antigens 2007;69 Suppl 1:153-5
85. Wang X, Jiang W, Zhang D. Association of 14-bp insertion/ deletion polymorphism of HLA-G gene with unexplained recurrent spontaneous abortion: A meta-Analysis. Tissue Antigens 2013;81:108-15
86. Suryanarayana V, Rao L, Kanakavalli M, Padmalatha V, Raseswari T, Deenadayal M, et al. Association between novel HLA-G genotypes and risk of recurrent miscarriages: A case-control study in a South Indian population. Reprod Sci 2008;15:817-24
87. Kolte AM, Steffensen R, Nielsen HS, Hviid TV, Christiansen OB. Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage. Hum Immunol 2010;71:482-8
88. Berger DS, Hogge WA, Barmada MM, Ferrell RE. Comprehensive analysis of HLA-G: Implications for recurrent spontaneous abortion. Reprod Sci 2010;17:331-8
89. Vargas RG, Sarturi PR, Mattar SB, Bompeixe EP, Silva Jdos S, Pirri A, et al. Association of HLA-G alleles and 3 UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples. Hum Immunol 2011;72:479-85
90. Christiansen OB, Kolte AM, Dahl M, Larsen EC, Steffensen R, Nielsen HS, et al. Maternal homozygocity for a 14 base pair insertion in exon 8 of the HLA-G gene and carriage of HLA class II alleles restricting HY immunity predispose to unexplained secondary recurrent miscarriage and low birth weight in children born to these patients. Hum Immunol 2012;73:699-705
91. Ober C, Aldrich CL, Chervoneva I, Billstrand C, Rahimov F, Gray HL, et al. Variation in the HLA-G promoter region influences miscarriage rates. Am J Hum Genet 2003;72:1425-35
92. Calicchio R, Doridot L, Miralles F, Mehats C, Vaiman D. DNA methylation, an epigenetic mode of gene expression regulation in reproductive science. Curr Pharm Des 2014;20:1726-50
93. Akhter A, Faridi RM, Das V, Pandey A, Naik S, Agrawal S. In vitro up-regulation of HLA-G using dexamethasone and hydrocortisone in first-trimester trophoblast cells of women experiencing recurrent miscarriage. Tissue Antigens 2012;80:126-35
94. Hviid TV, Christiansen OB. Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G-possible implications for human reproduction and autoimmune disease. Hum Immunol 2005;66:688-99
95. Witt CS, Goodridge J, Gerbase-Delima MG, Daher S, Christiansen FT. Maternal KIR repertoire is not associated with recurrent spontaneous abortion. Hum Reprod 2004;19:2653-7
96. Karhukorpi J, Laitinen T, Karttunen R, Tiilikainen AS. The functionally important IL-10 promoter polymorphism (-1082GA) is not a major genetic regulator in recurrent spontaneous abortions. Mol Hum Reprod 2001;7:201-3
97. Zammiti W, Mtiraoui N, Cochery-Nouvellon E, Mahjoub T, Almawi WY, Gris JC. Association of -592C/A, -819C/T and -1082A/ G interleukin-10 promoter polymorphisms with idiopathic recurrent spontaneous abortion. Mol Hum Reprod 2006;12:771-6
98. Unfried G, Bocskor S, Endler G, Nagele F, Huber JC, Tempfer CB. A polymorphism of the interleukin-6 gene promoter and idiopathic recurrent miscarriage. Hum Reprod 2003;18:267-70
99. Saijo Y, Sata F, Yamada H, Kondo T, Kato EH, Kishi R. Single nucleotide polymorphisms in the promoter region of the interleukin-6 gene and the risk of recurrent pregnancy loss in Japanese women. Fertil Steril 2004;81:374-8
100. Ma X, Xu LJ, Wang J, Xian MM, Liu M. Association of IL-1beta and IL-6 gene polymorphisms with recurrent spontaneous abortion in a Chinese Han population. Int J Immunogenet 2011;39:15-9
101. Unfried G, Tempfer C, Schneeberger C, Widmar B, Nagele F, Huber JC. Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage. Fertil Steril 2001;75:683-7
102. Karhukorpi J, Laitinen T, Kivela H, Tiilikainen A, Hurme M. IL-1 receptor antagonist gene polymorphism in recurrent spontaneous abortion. J Reprod Immunol 2003;58:61-7
103. Linjawi S, Li TC, Laird S, Blakemore A. Interleukin-1 receptor antagonist and interleukin-1 beta polymorphisms in women with recurrent miscarriage. Fertil Steril 2005;83:1549-52
104. Levrant S, Coulam CB, Jeyendran RS. Interleukin 1 receptor antagonist gene polymorphisms are not risk factors for recurrent pregnancy loss: Evaluation of couples. Am J Reprod Immunol 2008;60:224-8
105. Dai MZ, Pan YQ, Xu DP, Chen XJ, Qian RJ, Chen DH, et al. IL-1 receptor antagonist gene polymorphism in idiopathic recurrent spontaneous abortion in a Chinese Han population. Int J Immunogenet 2010;37:393-6
106. Traina E, Daher S, Moron AF, Sun SY, Franchim CS, Mattar R. Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion. J Reprod Immunol 2010;88:53-7
107. Saijo Y, Sata F, Yamada H, Konodo T, Kato EH, Kataoka S, et al. Interleukin-4 gene polymorphism is not involved in the risk of recurrent pregnancy loss. Am J Reprod Immunol 2004;52:143-6
108. Reid JG, Simpson NA, Walker RG, Economidou O, Shillito J, Gooi HC, et al. The carriage of pro-inflammatory cytokine gene polymorphisms in recurrent pregnancy loss. Am J Reprod Immunol 2001;45:35-40
109. Hefler LA, Tempfer CB, Unfried G, Schneeberger C, Lessl K, Nagele F, et al. A polymorphism of the interleukin-1beta gene and idiopathic recurrent miscarriage. Fertil Steril 2001;76:377-9
110. Wang ZC, Yunis EJ, De los Santos MJ, Xiao L, Anderson DJ, Hill JA. T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region. Genes Immun 2002;3:38-42
111. Babbage SJ, Arkwright PD, Vince GS, Perrey C, Pravica V, Quenby S, et al. Cytokine promoter gene polymorphisms and idiopathic recurrent pregnancy loss. J Reprod Immunol 2001;51:21-7
112. Alkhuriji AF, Alhimaidi AR, Babay ZA, Wary AS. The relationship between cytokine gene polymorphism and unexplained recurrent spontaneous abortion in Saudi females. Saudi Med J 2013;34:484-9
113. Messaoudi S, Al-Khateeb GM, Dendana M, Sater MS, Jazia KB, Nouira M, et al. (2011) Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage. Eur Cytokine Netw 2013;22:123-6
114. Le Bouteiller P, Tabiasco J. Killers become builders during pregnancy. Nat Med 2006;12:991-2
115. Hanna J, Goldman-Wohl D, Hamani Y, Avraham I, Greenfield C, Natanson-Yaron S, et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 2006;12:1065-74
116. Ostojic S, Volk M, Medica I, Kapovic M, Meden-Vrtovec H, Peterlin B. Polymorphisms in the interleukin-12/18 genes and recurrent spontaneous abortion. Am J Reprod Immunol 2007;58:403-8
117. Al-Khateeb GM, Sater MS, Finan RR, Mustafa FE, Al-Busaidi AS, Al-Sulaiti MA, et al. Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage. Fertil Steril 2011;96:921-6
118. Messaoudi S, Dandana M, Magdoud K, Meddeb S, Ben Slama N, Hizem S, et al. Interleukin-18 promoter polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population. J Reprod Immunol 2012;93:109-13
119. Bombell S, McGuire W. Cytokine polymorphisms in women with recurrent pregnancy loss: Meta-Analysis. Aust N Z J Obstet Gynaecol 2008;48:147-54
120. Medica I, Ostojic S, Pereza N, Kastrin A, Peterlin B. Association between genetic polymorphisms in cytokine genes and recurrent miscarriage-A meta-Analysis. Reprod Biomed Online 2009;19:406-14
121. Agrawal S, Parveen F, Faridi RM, Prakash S. Interleukin-1 gene cluster variants and recurrent pregnancy loss among North Indian women: Retrospective study and meta-Analysis. Reprod Biomed Online 2012;24:342-51
122. Sibai BM. Thrombophilia and severe preeclampsia: Time to screen and treat in future pregnancies? Hypertension 2005;46:1252-3
123. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science 2005;308:1592-4
124. Davenport WB, Kutteh WH. Inherited thrombophilias and adverse pregnancy outcomes: A review of screening patterns and recommendations. Obstet Gynecol Clin North Am 2014;41:133-44
125. Wang Z, Wang P, Wang X, He X, Xu D, Hu J, et al. Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: A systematic review and meta-Analysis. Metabolism 2013;62:1227-38
126. Rahimi Z, Aghaei A, Vaisi-Raygani A. AT2R -1332 G: A polymorphism and its interaction with AT1R 1166 A: C, ACE I/D and MMP-9 -1562 C: T polymorphisms: Risk factors for susceptibility to preeclampsia. Gene 2014;538:176-81
127. Martinelli I, Taioli E, Cetin I, Marinoni A, Gerosa S, Villa MV, et al. Mutations in coagulation factors in women with unexplained late fetal loss. N Engl J Med 2000;343:1015-8
128. Napoli C, Witztum JL, De Nigris F, Palumbo G, DArmiento FP, Palinski W. Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries. Circulation 1999;99:2003-10
129. 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
130. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: A meta-Analysis. Lancet 2003;361:901-8
131. Cao J, Cai J, Huang D, Han Q, Yang Q, Li T, et al. miR-335 represents an invasion suppressor gene in ovarian cancer by targeting Bcl-w. Oncol Rep 2013;30:701-6
132. Guerra-Shinohara EM, Bertinato JF, Tosin Bueno C, Cordeiro da Silva K, Burlacchini De Carvalho MH, Pulcineli Vieira Francisco R, et al. Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss. Thromb Haemost 2013;108:693-700
133. Li W, Zeng Chan W, Cui X, Xiao Feng L, Mao Sheng Y. Genome-wide screening for risk Loci of idiopathic recurrent miscarriage in a Han Chinese population: A pilot study. Reprod Sci 2010;17:578-84
134. Kolte AM, Nielsen HS, Moltke I, Degn B, Pedersen B, Sunde L, et al. A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage. Mol Hum Reprod 2011;17:379-85
135. Christiansen OB, Riisom K, Lauritsen JG, Grunnet N, Jersild C. Association of maternal HLA haplotypes with recurrent spontaneous abortions. Tissue Antigens 1989;34:190-9
136. Kluijtmans LA, Kastelein JJ, Lindemans J, Boers GH, Heil SG, Bruschke AV, et al. Thermolabile methylenetetrahydrofolate reductase in coronary artery disease. Circulation 1997;96:2573-7
137. Nelen WL, Van Der Molen EF, Blom HJ, Heil SG, Steegers EA, Eskes TK. Recurrent early pregnancy loss and genetic-related disturbances in folate and homocysteine metabolism. Br J Hosp Med 1997;58:511-3
138. Mercier E, Lissalde-Lavigne G, Gris JC. JAK2 V617F mutation in unexplained loss of first pregnancy. N Engl J Med 2007;357:1984-5
139. Laissue P, Burgio G, lHote D, Renault G, Marchiol-Fournigault C, Fradelizi D, et al. Identification of Quantitative Trait Loci responsible for embryonic lethality in mice assessed by ultrasonography. Int J Dev Biol 2009;53:623-9
140. Vatin M, Bouvier S, Bellazi L, Montagutelli X, Laissue P, Ziyyat A, et al. Polymorphisms of human placental alkaline phosphatase are associated with in vitro fertilization success and recurrent pregnancy loss. Am J Pathol 2014;184:362-8
141. Cohen D, Buurma A, Goemaere NN, Girardi G, le Cessie S, Scherjon S, et al. Classical complement activation as a footprint for murine and human antiphospholipid antibody-induced fetal loss. J Pathol 2011;225:502-11
142. Girardi G, Salmon JB. The role of complement in pregnancy and fetal loss. Autoimmunity 2003;36:19-26
143. Wu X, Spitzer D, Mao D, Peng SL, Molina H, Atkinson JP. Membrane protein Crry maintains homeostasis of the complement system. J Immunol 2008;181:2732-40
144. Pedroni SM, Gonzalez JM, Wade J, Jansen MA, Serio A, Marshall I, et al. Complement inhibition and statins prevent fetal brain cortical abnormalities in a mouse model of preterm birth. Biochim Biophys Acta 2014;1842:107-15
145. Takeshita A, Kusakabe KT, Hiyama M, Kuniyoshi N, Kondo T, Kano K, et al. Dynamics and reproductive effects of complement factors in the spontaneous abortion model of CBA/JxDBA/2 mice. Immunobiology 2014;219:385-91