Obstet Gynecol Sci.  2019 Jul;62(4):212-223. 10.5468/ogs.2019.62.4.212.

Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects

Affiliations
  • 1Department of Biomedical Science, CHA University, CHA General Hospital, Seongnam, Korea, Seoul, Korea. baek@cha.ac.kr
  • 2Department of Obstetrics and Gynecology, Ewha Womans University College of Medicine, Seoul, Korea.

Abstract

Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.

Keyword

Proteomics; Recurrent miscarriage; Vitamin D

MeSH Terms

Abortion, Habitual
Abortion, Spontaneous
Colony-Stimulating Factors
Embryo Implantation
Embryonic Development
Female
Fertilization
Fetal Development
Gene Expression
Glucose
Humans
Inflammation
Killer Cells, Natural
Metabolism
MicroRNAs
Obstetrics
Pregnancy*
Proteomics
T-Lymphocytes
Tumor Necrosis Factor-alpha
Vitamin D
Colony-Stimulating Factors
Glucose
MicroRNAs
Tumor Necrosis Factor-alpha
Vitamin D

Figure

  • Fig. 1 Role of natural killer (NK) cells in creating a supporting environment for embryo implantation. T cell immunoglobulin (type I membrane protein) and mucin-containing protein 3+ uterine NK cells combine with ligand galectin-9 (Gal-9) to secrete interleukin (IL)-4, transforming growth factor (TGF)-β, IL-10, with decreased production of tumor necrosis factor (TNF)-α, thereby inducing immune suppression and tolerance, and creating an environment conducive to embryo implantation.

  • Fig. 2 Effect of activated vitamin D on immune cells. Activated vitamin D stimulates T helper (Th)2 cells to secrete anti-inflammatory factors, promotes T-reg cell differentiation and proliferation, and increases the number of CD8+ cells. Activated vitamin D stimulates Th1 cells and Th17 cells to secrete pro-inflammatory factors, and increase the function/number of CD4+ cells. TNF, tumor necrosis factor; IFN, interferon; IL, interleukin.


Reference

1. Krieg S, Westphal L. Immune function and recurrent pregnancy loss. Semin Reprod Med. 2015; 33:305–312.
Article
2. Coulam CB, Clark DA, Beer AE, Kutteh WH, Silver R, Kwak J, et al. Current clinical options for diagnosis and treatment of recurrent spontaneous abortion. Clinical guidelines recommendation committee for diagnosis and treatment of recurrent spontaneous abortion. Am J Reprod Immunol. 1997; 38:57–74.
3. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012; 98:1103–1111.
4. Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013; 99:63.
5. Pan HT, Ding HG, Fang M, Yu B, Cheng Y, Tan YJ, et al. Proteomics and bioinformatics analysis of altered protein expression in the placental villous tissue from early recurrent miscarriage patients. Placenta. 2018; 61:1–10.
Article
6. Kim YS, Kim MS, Lee SH, Choi BC, Lim JM, Cha KY, et al. Proteomic analysis of recurrent spontaneous abortion: identification of an inadequately expressed set of proteins in human follicular fluid. Proteomics. 2006; 6:3445–3454.
Article
7. Kim MS, Gu BH, Song S, Choi BC, Cha DH, Baek KH. ITI-H4, as a biomarker in the serum of recurrent pregnancy loss (RPL) patients. Mol Biosyst. 2011; 7:1430–1440.
Article
8. Li L, Choi BC, Ryoo JE, Song SJ, Pei CZ, Lee KY, et al. Opposing roles of inter-α-trypsin inhibitor heavy chain 4 in recurrent pregnancy loss. EBioMedicine. 2018; 37:535–546.
Article
9. Tyers M, Mann M. From genomics to proteomics. Nature. 2003; 422:193–197.
Article
10. Jeon YJ, Kim JH, Lee BE, Rah H, Shin JE, Kang H, et al. Association between polymorphisms in the renin-angiotensin system genes and prevalence of spontaneously aborted fetuses. Am J Reprod Immunol. 2013; 70:238–245.
Article
11. Bell CE, Larivière NM, Watson PH, Watson AJ. Mitogen-activated protein kinase (MAPK) pathways mediate embryonic responses to culture medium osmolarity by regulating Aquaporin 3 and 9 expression and localization, as well as embryonic apoptosis. Hum Reprod. 2009; 24:1373–1386.
Article
12. Vergnes L, Péterfy M, Bergo MO, Young SG, Reue K. Lamin B1 is required for mouse development and nuclear integrity. Proc Natl Acad Sci U S A. 2004; 101:10428–10433.
Article
13. Nagatomo H, Kohri N, Akizawa H, Hoshino Y, Yamauchi N, Kono T, et al. Requirement for nuclear autoantigenic sperm protein mRNA expression in bovine preimplantation development. Anim Sci J. 2016; 87:457–461.
Article
14. Stary M, Pasteiner W, Summer A, Hrdina A, Eger A, Weitzer G. Parietal endoderm secreted SPARC promotes early cardiomyogenesis in vitro . Exp Cell Res. 2005; 310:331–343.
15. Stary M, Schneider M, Sheikh SP, Weitzer G. Parietal endoderm secreted S100A4 promotes early cardiomyogenesis in embryoid bodies. Biochem Biophys Res Commun. 2006; 343:555–563.
Article
16. Wang X, Chang Y, Li Y, Zhang X, Goodrich DW. Thoc1/Hpr1/p84 is essential for early embryonic development in the mouse. Mol Cell Biol. 2006; 26:4362–4367.
Article
17. Chávez S, Beilharz T, Rondón AG, Erdjument-Bromage H, Tempst P, Svejstrup JQ, et al. A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. EMBO J. 2000; 19:5824–5834.
18. Rehwinkel J, Herold A, Gari K, Köcher T, Rode M, Ciccarelli FL, et al. Genome-wide analysis of mRNAs regulated by the THO complex in Drosophila melanogaster. Nat Struct Mol Biol. 2004; 11:558–566.
Article
19. Jakupoglu C, Przemeck GK, Schneider M, Moreno SG, Mayr N, Hatzopoulos AK, et al. Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol Cell Biol. 2005; 25:1980–1988.
Article
20. Brafman DA, Phung C, Kumar N, Willert K. Regulation of endodermal differentiation of human embryonic stem cells through integrin-ECM interactions. Cell Death Differ. 2013; 20:369–381.
Article
21. Frésard L, Morisson M, Brun JM, Collin A, Pain B, Minvielle F, et al. Epigenetics and phenotypic variability: some interesting insights from birds. Genet Sel Evol. 2013; 45:16.
Article
22. Wu H, Zhang Y. Early embryos reprogram DNA methylation in two steps. Cell Stem Cell. 2012; 10:487–489.
Article
23. Blair JD, Yuen RK, Lim BK, McFadden DE, von Dadelszen P, Robinson WP. Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia. Mol Hum Reprod. 2013; 19:697–708.
Article
24. Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007; 447:433–440.
Article
25. Reamon-Buettner SM, Borlak J. A new paradigm in toxicology and teratology: altering gene activity in the absence of DNA sequence variation. Reprod Toxicol. 2007; 24:20–30.
Article
26. Hanna CW, McFadden DE, Robinson WP. DNA methylation profiling of placental villi from karyotypically normal miscarriage and recurrent miscarriage. Am J Pathol. 2013; 182:2276–2284.
Article
27. Yu M, Du G, Xu Q, Huang Z, Huang X, Qin Y, et al. Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy loss. EBioMedicine. 2018; 35:334–344.
Article
28. Long X, Li Y, Qiu S, Liu J, He L, Peng Y. MiR-582-5p/miR-590-5p targeted CREB1/CREB5-NF-κB signaling and caused opioid-induced immunosuppression in human monocytes. Transl Psychiatry. 2016; 6:e757.
Article
29. Nevalainen T, Kananen L, Marttila S, Jylhä M, Hervonen A, Hurme M, et al. Transcriptomic and epigenetic analyses reveal a gender difference in aging-associated inflammation: the vitality 90+ study. Age (Dordr). 2015; 37:9814.
Article
30. Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol. 2007; 8:277–284.
Article
31. Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature. 2007; 445:766–770.
Article
32. Hou W, Li Z, Li Y, Fang L, Li J, Huang J, et al. Correlation between protein expression of FOXP3 and level of FOXP3 promoter methylation in recurrent spontaneous abortion. J Obstet Gynaecol Res. 2016; 42:1439–1444.
Article
33. Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012; 18:1754–1767.
Article
34. White MD, Plachta N. How adhesion forms the early mammalian embryo. Curr Top Dev Biol. 2015; 112:1–17.
Article
35. Quintero-Ronderos P, Mercier E, Fukuda M, González R, Suárez CF, Patarroyo MA, et al. Novel genes and mutations in patients affected by recurrent pregnancy loss. PLoS One. 2017; 12:e0186149.
Article
36. Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol. 1997; 272:R441–63.
Article
37. 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; 274:119–124.
Article
38. 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; 152:64–67.
39. Azani A, Hosseinzadeh A, Azadkhah R, Zonouzi AA, Zonouzi AP, Aftabi Y, et al. Association of endothelial nitric oxide synthase gene variants (-786 T>C, intron 4 b/a VNTR and 894 G>T) with idiopathic recurrent pregnancy loss: a case-control study with haplotype and in silico analysis. Eur J Obstet Gynecol Reprod Biol. 2017; 215:93–100.
40. Ryu CS, Sakong JH, Ahn EH, Kim JO, Ko D, Kim JH, et al. Association study of the three functional polymorphisms (TAS2R46G>A, OR4C16G>A, and OR4X1A>T) with recurrent pregnancy loss. Genes Genomics. 2019; 41:61–70.
41. Trowsdale J, Betz AG. Mother's little helpers: mechanisms of maternal-fetal tolerance. Nat Immunol. 2006; 7:241–246.
Article
42. Schjenken JE, Zhang B, Chan HY, Sharkey DJ, Fullston T, Robertson SA. Mirna regulation of immune tolerance in early pregnancy. Am J Reprod Immunol. 2016; 75:272–280.
Article
43. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010; 63:601–610.
Article
44. Kheshtchin N, Gharagozloo M, Andalib A, Ghahiri A, Maracy MR, Rezaei A. The expression of Th1- and Th2-related chemokine receptors in women with recurrent miscarriage: the impact of lymphocyte immunotherapy. Am J Reprod Immunol. 2010; 64:104–112.
Article
45. Nakagawa K, Kwak-Kim J, Ota K, Kuroda K, Hisano M, Sugiyama R, et al. Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood TH1/TH2 cell ratios. Am J Reprod Immunol. 2015; 73:353–361.
Article
46. Ota K, Dambaeva S, Han AR, Beaman K, Gilman-Sachs A, Kwak-Kim J. Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum Reprod. 2014; 29:208–219.
Article
47. Wegmann TG. Placental immunotrophism: maternal T cells enhance placental growth and function. Am J Reprod Immunol Microbiol. 1987; 15:67–69.
Article
48. Li Y, Zhang J, Zhang D, Hong X, Tao Y, Wang S, et al. Tim-3 signaling in peripheral nk cells promotes maternal-fetal immune tolerance and alleviates pregnancy loss. Sci Signal. 2017; 10:eaah4323.
Article
49. Motedayyen H, Rezaei A, Zarnani AH, Tajik N. Human amniotic epithelial cells inhibit activation and pro-inflammatory cytokines production of naive CD4+ T cells from women with unexplained recurrent spontaneous abortion. Reprod Biol. 2018; 18:182–188.
Article
50. Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes. 1993; 42:359–362.
Article
51. Alecsandru D, Barrio A, Andia V, Cruz E, Aparicio P, Serna J, et al. Pancreatic autoimmunity: an unknown etiology on patients with assisted reproductive techniques (ART)-recurrent reproductive failure. PLoS One. 2018; 13:e0203446.
Article
52. Pedicino D, Liuzzo G, Trotta F, Giglio AF, Giubilato S, Martini F, et al. Adaptive immunity, inflammation, and cardiovascular complications in type 1 and type 2 diabetes mellitus. J Diabetes Res. 2013; 2013:184258.
Article
53. Yang Z, Zhou Z, Huang G, Ling H, Yan X, Peng J, et al. The CD4(+) regulatory T-cells is decreased in adults with latent autoimmune diabetes. Diabetes Res Clin Pract. 2007; 76:126–131.
Article
54. Akesson C, Uvebrant K, Oderup C, Lynch K, Harris RA, Lernmark A, et al. Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency. Clin Exp Immunol. 2010; 161:48–56.
55. Buzzetti R, Di Pietro S, Giaccari A, Petrone A, Locatelli M, Suraci C, et al. High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Diabetes Care. 2007; 30:932–938.
Article
56. Ruuls SR, Sedgwick JD. Unlinking tumor necrosis factor biology from the major histocompatibility complex: lessons from human genetics and animal models. Am J Hum Genet. 1999; 65:294–301.
Article
57. Majetschak M, Obertacke U, Schade FU, Bardenheuer M, Voggenreiter G, Bloemeke B, et al. Tumor necrosis factor gene polymorphisms, leukocyte function, and sepsis susceptibility in blunt trauma patients. Clin Diagn Lab Immunol. 2002; 9:1205–1211.
Article
58. Siwetz M, Blaschitz A, El-Heliebi A, Hiden U, Desoye G, Huppertz B, et al. TNF-α alters the inflammatory secretion profile of human first trimester placenta. Lab Invest. 2016; 96:428–438.
Article
59. Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science. 2002; 296:1634–1635.
Article
60. Trussell J, Lalla AM, Doan QV, Reyes E, Pinto L, Gricar J. Cost effectiveness of contraceptives in the United States. Contraception. 2009; 79:5–14.
Article
61. Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med. 2010; 16:452–459.
Article
62. Alijotas-Reig J, Llurba E, Gris JM. Potentiating maternal immune tolerance in pregnancy: a new challenging role for regulatory T cells. Placenta. 2014; 35:241–248.
Article
63. Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016; 75:795–810.
Article
64. Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016; 55:1693–1697.
65. 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.
Article
66. Kauma SW, Aukerman SL, Eierman D, Turner T. Colony-stimulating factor-1 and c-fms expression in human endometrial tissues and placenta during the menstrual cycle and early pregnancy. J Clin Endocrinol Metab. 1991; 73:746–751.
67. Rahmati M, Petitbarat M, Dubanchet S, Bensussan A, Chaouat G, Ledee N. Colony stimulating factors 1, 2, 3 and early pregnancy steps: from bench to bedside. J Reprod Immunol. 2015; 109:1–6.
Article
68. Makinoda S, Hirosaki N, Waseda T, Tomizawa H, Fujii R. Granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation and its clinical usefulness. Curr Med Chem. 2008; 15:604–613.
69. Mielcarek M, Graf L, Johnson G, Torok-Storb B. Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation. Blood. 1998; 92:215–222.
Article
70. Sugita K, Hayakawa S, Karasaki-Suzuki M, Hagiwara H, Chishima F, Aleemuzaman S, et al. Granulocyte colony stimulation factor (G-CSF) suppresses interleukin (IL)-12 and/or IL-2 induced interferon (IFN)-gamma production and cytotoxicity of decidual mononuclear cells. Am J Reprod Immunol. 2003; 50:83–89.
71. Moldenhauer LM, Keenihan SN, Hayball JD, Robertson SA. GM-CSF is an essential regulator of T cell activation competence in uterine dendritic cells during early pregnancy in mice. J Immunol. 2010; 185:7085–7096.
Article
72. Wright EM, Ghezzi C, Loo DD. Novel and unexpected functions of sglts. Physiology (Bethesda). 2017; 32:435–443.
Article
73. Faham S, Watanabe A, Besserer GM, Cascio D, Specht A, Hirayama BA, et al. The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport. Science. 2008; 321:810–814.
Article
74. Salker MS, Singh Y, Zeng N, Chen H, Zhang S, Umbach AT, et al. Loss of endometrial sodium glucose cotransporter sglt1 is detrimental to embryo survival and fetal growth in pregnancy. Sci Rep. 2017; 7:12612.
Article
75. Shibazaki T, Tomae M, Ishikawa-Takemura Y, Fushimi N, Itoh F, Yamada M, et al. KGA-2727, a novel selective inhibitor of a high-affinity sodium glucose cotransporter (SGLT1), exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther. 2012; 342:288–296.
Article
76. Sharma P, Khairnar V, Madunić IV, Singh Y, Pandyra A, Salker MS, et al. Sglt1 deficiency turns listeria infection into a lethal disease in mice. Cell Physiol Biochem. 2017; 42:1358–1365.
Article
77. Kitaya K, Takeuchi T, Mizuta S, Matsubayashi H, Ishikawa T. Endometritis: new time, new concepts. Fertil Steril. 2018; 110:344–350.
Article
78. McQueen DB, Perfetto CO, Hazard FK, Lathi RB. Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy loss. Fertil Steril. 2015; 104:927–931.
Article
79. Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. Am J Reprod Immunol. 2011; 66:410–415.
Article
80. Cicinelli E, Matteo M, Trojano G, Mitola PC, Tinelli R, Vitagliano A, et al. Chronic endometritis in patients with unexplained infertility: prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol. 2018; 79:e12782.
Article
81. Metwally M, Preece R, Thomas J, Ledger W, Li TC. A proteomic analysis of the endometrium in obese and overweight women with recurrent miscarriage: preliminary evidence for an endometrial defect. Reprod Biol Endocrinol. 2014; 12:75.
Article
82. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998; 83:3078–3082.
Article
83. Okon MA, Laird SM, Tuckerman EM, Li TC. Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function. Fertil Steril. 1998; 69:682–690.
Article
84. Rahman TU, Ullah K, Guo MX, Pan HT, Liu J, Ren J, et al. Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages. Oncotarget. 2018; 9:24627–24641.
Article
85. Practice Committee of the American Society for Reproductive Medicine. Current clinical irrelevance of luteal phase deficiency: a committee opinion. Fertil Steril. 2015; 103:e27–e32.
86. Amrane S, McConnell R. Endocrine causes of recurrent pregnancy loss. Semin Perinatol. 2019; 43:80–83.
Article
87. Meresman GF, Olivares C, Vighi S, Alfie M, Irigoyen M, Etchepareborda JJ. Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients. Reprod Biol Endocrinol. 2010; 8:126.
Article
88. Licht P, Fluhr H, Neuwinger J, Wallwiener D, Wildt L. Is human chorionic gonadotropin directly involved in the regulation of human implantation? Mol Cell Endocrinol. 2007; 269:85–92.
Article
89. Fox C, Azores-Gococo D, Swart L, Holoch K, Savaris RF, Likes CE, et al. Luteal phase HCG support for unexplained recurrent pregnancy loss - a low hanging fruit? Reprod Biomed Online. 2017; 34:319–324.
Article
90. Teichert A, Arnold LA, Otieno S, Oda Y, Augustinaite I, Geistlinger TR, et al. Quantification of the vitamin D receptor-coregulator interaction. Biochemistry. 2009; 48:1454–1461.
Article
91. Shahbazi M, Jeddi-Tehrani M, Zareie M, Salek-Moghaddam A, Akhondi MM, Bahmanpoor M, et al. Expression profiling of vitamin D receptor in placenta, decidua and ovary of pregnant mice. Placenta. 2011; 32:657–664.
Article
92. Grzechocinska B, Dabrowski FA, Cyganek A, Wielgos M. The role of vitamin D in impaired fertility treatment. Neuroendocrinol Lett. 2013; 34:756–762.
93. Lemire JM, Adams JS, Sakai R, Jordan SC. 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest. 1984; 74:657–661.
Article
94. Piccinni MP, Scaletti C, Maggi E, Romagnani S. Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol. 2000; 109:30–33.
Article
95. Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab. 2008; 4:80–90.
Article
96. Ji JL, Muyayalo KP, Zhang YH, Hu XH, Liao AH. Immunological function of vitamin D during human pregnancy. Am J Reprod Immunol. 2017; 78:e12716.
Article
97. Morales-Prieto DM, Chaiwangyen W, Ospina-Prieto S, Schneider U, Herrmann J, Gruhn B, et al. MicroRNA expression profiles of trophoblastic cells. Placenta. 2012; 33:725–734.
Article
98. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136:215–233.
Article
99. Parveen F, Agrawal S. Recurrent miscarriage and micro-RNA among north Indian women. Reprod Sci. 2015; 22:410–415.
Article
100. Fluhr H, Wenig H, Spratte J, Heidrich S, Ehrhardt J, Zygmunt M. Non-apoptotic fas-induced regulation of cytokines in undifferentiated and decidualized human endometrial stromal cells depends on caspase-activity. Mol Hum Reprod. 2011; 17:127–134.
Article
101. Carcagno AL, Marazita MC, Ogara MF, Ceruti JM, Sonzogni SV, Scassa ME, et al. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation. PLoS One. 2011; 6:e21938.
Article
102. Jeon YJ, Choi YS, Rah H, Kim SY, Choi DH, Cha SH, et al. Association study of microRNA polymorphisms with risk of idiopathic recurrent spontaneous abortion in Korean women. Gene. 2012; 494:168–173.
Article
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