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Mouse is the new woman? Translational research in reproductive immunology

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Abstract

In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother’s immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother’s exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models. The artificially induced model of endometriosis (which contributes to infertility) is also compared to what occurs in women. One may conclude that the female mouse provides a good analog of the human female. Nevertheless, it is always important to validate mouse data with human studies. The discussion focuses on the intrauterine interface between embryonic and placental tissues and maternal uterine tissues and the dialogue that is referred to as cross-talk. Issues relating to bidirectional transplacental traffic of immune system cells are not discussed as there is very little relevant data.

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Abbreviations

APC:

Antigen-presenting cell

EVT:

Extravillous trophoblasts

EVTP:

Endovascular trophoblast plugs

NK:

Natural killer

uNK:

Uterine NK cell subdivided into‚ true uterine NK cells (TuNKs) and‚ blood-type uterine NK cells (BuNKs)

PMNL:

Polymorphonuclear leukocyte or neutrophil

IVIG:

Intravenous immunoglobilin G

LIT:

Mononuclear leukocyte immunotherapy

hCG:

Human chorionic gonadotropin

sflt-1:

Soluble VEGF receptor

Teff:

Effector T cell

Tregs:

Regulatory T cells

TcR:

T cell receptor

IVFET:

In vitro fertilization and embryo transfer

MHC:

Major histocompatibility complex (antigens)

KIR:

Killer-cell immunoglobulin-like receptors

IUGR:

Intrauterine growth restriction

RIF:

Recurrent implantation failure

RSA:

Recurrent spontaneous abortion

CSF:

Colony stimulating factor

References

  1. Clark DA (2014) The use and misuse of animal analog models of human pregnancy disorders. J Reprod Immunol 103:1–8

    Article  CAS  PubMed  Google Scholar 

  2. Hamilton WJ, Boyd JD, Mossman HW (1962) Human Embryology, 3rd edn. Heffer, Cambridge

    Google Scholar 

  3. Burton GJ, Jauniaux E, Watson AL (1999) Maternal arterial connections to the placental intervillous spaces during the first trimester of pregnancy: the Boyd collection revisited. Am J Obstet Gynecol 181:718–724

    Article  CAS  PubMed  Google Scholar 

  4. Doherty PC, Zinkernagel RM (1975) Enhanced immunological surveillance in mice heterozygous for the H-2 gene complex. Nature 256:50–52

    Article  CAS  PubMed  Google Scholar 

  5. Medawar PB (1953) Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp Soc Exp Biol Med 7:320–338

    Google Scholar 

  6. Clark DA, Chaouat G (1989) What do we know about spontaneous abortion mechanisms? Am J Reprod Immunol Microbiol 19:28–37

    Article  CAS  Google Scholar 

  7. Clark DA (2014) Popular myths in reproductive immunology. J Reprod Immunol 104–105:54–62

    Article  PubMed  CAS  Google Scholar 

  8. Potts WK, Manning CJ, Wakeland EK (1991) Mating patterns in seminatural populations of mice influenced by MHC genotype. Nature 352:619–621

    Article  CAS  PubMed  Google Scholar 

  9. Moffett A, Loke C (2006) Immunology of placentation in eutherian mammals. Nat Rev Immunol 6:584–594

    Article  CAS  PubMed  Google Scholar 

  10. Rossant J, Cross JC (2001) Placental development: lessons learned from mouse mutants. Nat Rev Genet 2:538–548

    Article  CAS  PubMed  Google Scholar 

  11. Redline RW, Lu CY (1989) Localization of fetal major histocompatibility complex antigens and maternal leukocytes in murine placenta. Implications for maternal-fetal immunological relationship. Lab Invest 61:27–36

    CAS  PubMed  Google Scholar 

  12. Clark DA, Petitbarat M, Chaouat G (2008) How should data on murine spontaneous abortion rates be expressed and analysed? Am J Reprod Immunol 60:192–196

    Article  PubMed  Google Scholar 

  13. Clark DA (2003) Is there any evidence for immunologically-mediated or immunologically modifiable early pregnancy failure? J Assist Reprod Genet 20:63–72

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mertzanidou A, Wilton L, Cheng J, Spits C, Vanneste E, Moreau Y, Vermeesch JR, Sermon K (2013) Microarray analysis reveals abnormal chromosomal components in over 70% of 14 normally developing human embryos. Hum Reprod 28:256–264

    Article  CAS  PubMed  Google Scholar 

  15. Roberts CI, Lowe CR (1975) Where have all the conceptions gone? Lancet 1:498–499

    Article  Google Scholar 

  16. Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C, Debrock S, Amyere N, Vikkula M, Schuit F, Fryns J-P, Verbeje G, D’Hooghe T, Moreau Y, Vermeesche JR (2009) Chromosome instability is common in human cleavage-stage embryos. Nat Med 15:577–583

    Article  CAS  PubMed  Google Scholar 

  17. Brosens JJ, Gellersen B (2010) Something new about early pregnancy: decidual biosensoring and natural embryo selection. Ultrasound Obstet Gynecol 36:1–5

    Article  CAS  PubMed  Google Scholar 

  18. Lea RG, Clark DA (1991) Macrophages and migratory cells in endometrium relevant to implantation. In: Seppalla W (ed). Bailliers Clinical Obstet Gynecol pp 25–59.

  19. Chaouat G, Kiger N, Wegmann T (1983) Vaccination against spontaneous abortion in mice. J Reprod Immunol 5:389–392

    Article  CAS  PubMed  Google Scholar 

  20. Cha J, Bartos A, Park C, Sun X, Li Y, Cha S-W, Ajima R, Ho H-YH, Yamaguchi TP, Dey SK (2014) Appropriate crypt formation in the uterus fro embryo homing and implantation requires Wnt5a-ROR signaling. Cell Rep 8:382–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Peng J, Monsivais D, You R, Zhong H, Pangas SA, Matzuk MM (2015) Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and placental development. Proc Natl Acad Sci U S A 11(36):E5098–E5107. doi:10.1073/pnas.1514498112

    Article  CAS  Google Scholar 

  22. Wakuda K, Takakura K, Nakanishi K, Kita N, Shi H, Hirose M, Noda Y (1999) Embryo-dependent induction of embryo receptivity in the mouse endometrium. J Reprod Fertil 115:315–324

    Article  CAS  PubMed  Google Scholar 

  23. Mossman HW (1983) Vertebrate fetal membranes. McMillan

  24. Parr EL, Blanden RV, Tulsi RS (1980) Epithelium of mouse yolk sac placenta lacks H-2 complex alloantigens. J Exp Med 152:945–955

    Article  CAS  PubMed  Google Scholar 

  25. Plaks V, Birnberg T, Berkutzki T, Sela S, Ben Yashar A, Kalchenko V, Mor G, Keshet E, Dekel N, Neeman M, Jung S (2008) Uterine DCs are crucial for decidua formation during embryo implantation in mice. J Clin Invest 118:3954–3965

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Pollard JW (2008) Uterine DCs are essential for pregnancy. J Clin Invest 118:2832–2835

    Google Scholar 

  27. Chaouat G, Dubanchet S, Lydee N (2007) Cytokines: important for implantation? J Assist Reprod Genet 24:491–505

    Article  PubMed  PubMed Central  Google Scholar 

  28. Croy BA, Chen Z, Hofmann AP, Lord EM, Sedlacek AL, Gerber SA (2012) Imaging of vascular development in early mouse decidua and its association with lymphocytes and trophoblasts. Biol Reprod 87:125. doi:10.1095/biolreprod.1132.12830

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Cory BA (2009) Interferon gamma in successful pregnancies. Biol Reprod 80:848–859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carayannopoulos LN, Barks JL, Yokayama WM, Riley JK (2010) Murine trophoblast cells induce NK cell interferon-gamma production through KLRK1. Biol Reprod 83:404–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ahmed A, Singh J, Khan Y, Seshan SV, Girardi G (2010) A new mouse model to explore therapies for preeclampsia. PLoS ONE 5:e13663. doi:10.1371/journal.pone.0012663

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Barber EM, Pollard JW (2003) The uterine NK cell population requires IL-15 but these cells are not required for pregnancy nor the resolution of a Listeria monocytogenes infection. J Immunol 171:37–46

    Article  CAS  PubMed  Google Scholar 

  33. Wilcox AJ, Baird DD, Weinberg CR (1999) Time of implantation of the conceptus and loss of pregnancy. N Engl J Med 340:1796–1799

    Article  CAS  PubMed  Google Scholar 

  34. Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M, Fisher SJ (2004) Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest 114:744–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hempstock J, Jauniaux E, Greenwold N, Burton GJ (2003) The contribution of placental oxidative stress to early pregnancy failure. Hum Pathol 34:1265–1275

    Article  CAS  PubMed  Google Scholar 

  36. Ledee-Battaille N, Lapree-Delage G, Taupin JL, Dubanchet S, Frydman R, Chaouat G (2002) Concentration of leukemia inhibitory factor (LIF) in uterine flushing fluid is highly predictive of embryo implantation. Hum Reprod 17:213–218

    Article  Google Scholar 

  37. Oger P, Bulla R, Tedesco F, Portier A, Dubanschet S, Bally M, Wainer R, Chaouat G, Ledee N (2009) Higher interleukin-18 and mannose-binding lectin are present in uterine lumen of patients with unexplained infertility. Reprod Biomed Online 19:591–598

    Article  CAS  PubMed  Google Scholar 

  38. Hey NA, Li TC, Devine PL, Graham RA, Saravelos H, Aplin JD (1995) MUC1 in secretory phase endometrium: expression in precisely dated biopsies and flushings from normal and recurrent miscarriage patients. Hum Reprod 10:2655–2662

    CAS  PubMed  Google Scholar 

  39. Lachapelle MH, Miron P, Hemmings R, Roy DC (1996) Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. J Immunol 156:4027–4034

    CAS  PubMed  Google Scholar 

  40. Tuckerman E, Mariee N, Prakash A, Li TC, Laird S (2010) Uterine natural killer cells in peri-implantation endometrium from women with repeated implantation failure after IVF. J Reprod Immunol 87:60–66

    Article  CAS  PubMed  Google Scholar 

  41. Coulam CB, Stephenson M, Stern JJ, Clark DA (1996) Immunotherapy for recurrent pregnancy loss: Analysis of results from clinical trials. Am J Reprod Immunol 35:352–359

    Article  CAS  PubMed  Google Scholar 

  42. Quenby S, Bates M, Doig T, Brerwster J, Lewis-Jones DI, Johnson PM, Vince G (1999) Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod 14:2386–2391

    Article  CAS  PubMed  Google Scholar 

  43. Quenby S, Anim-Somuah M, Kalumbi C, Farquharsom R, Aplin JD (2007) Different types of recurrent miscarriage are associated with varying patterns of adhesion molecule expression in endometrium. Reprod Biomed Online 14:224–234

    Article  CAS  PubMed  Google Scholar 

  44. Karimzadeh MA, Ayazi Rosbahani M, Tabibnejad N (2009) Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilization/intracytoplasmic sperm injection: a randomized clinical trial. Aust N Zeland J Obstet Gynecol 49:677–680

    Article  Google Scholar 

  45. Daya S (1987) Human chorionic gonadotropin increase in normal early pregnancy. Am J Obstet Gynecol 156:286–290

    Article  CAS  PubMed  Google Scholar 

  46. Cole LA (2012) Hyperglycosylated hCG and pregnancy failures. J Reprod Immunol 93:119–122

    Article  CAS  PubMed  Google Scholar 

  47. Sasaki Y, Ladner DG, Cole LA (2008) Hyperglycosylated human chorionic gonadotropin and the source of pregnancy failures. Fertil Steril 89:1781–1786

    Article  CAS  PubMed  Google Scholar 

  48. Guibourdenche J, Handschuh K, Tsatsaeis V, Gerbaud P, Leguy MC, Muller F, Evian Brion D, Fournier T (2010) Hyperglycosylated jCG is a marker of early human trophoblast invasion. J Clin Endocrinol Metab 95:E240–E344

    Article  CAS  PubMed  Google Scholar 

  49. Hedley ML, Drake BL, Head JR, Tucker PW, Forman J (1989) Differential expression of the class 1 MHC genes in the embryo and placenta during midgestational development in the mouse. J Immunol 142:4046–4053

    CAS  PubMed  Google Scholar 

  50. Fukui A, Kwak-Kim J, Nitrivales E, Gillman-Sachs A, Lee SK, Beaman K (2008) Intracellular cytokine expression of peripheral blood natural killer cell subsets with recurrent spontaneous abortions and implantation failures. Fertil Steril 89:157–165

    Article  CAS  PubMed  Google Scholar 

  51. Kwak-Kim J, Gilman-Sachs A, Kim CE (2005) T helper 1 and 2 immune responses in relationship to pregnancy, nonpregnancy, recurrent spontaneous abortions and infertility of repeated implantation failures. Chem Immunol Allergy 88:64–79

    CAS  PubMed  Google Scholar 

  52. Yang KM, Nitrivalas E, Cho HJ, Kim NY, Beaman K, Gillman-Sachs A, Kwak-Kim J (2010) Women with multiple implantation failures and recurrent pregnancy losses have increased peripheral blood T cell activation. Am J Reprod Immunol 63:370–378

    Article  CAS  PubMed  Google Scholar 

  53. Lee SK, Kim JY, Hur SE, Na BJ, Lee M, Fukui A, Gilman-Sachs A, Kwak-Kim J (2011) Foxp3(high) and Foxp3(low) Treg cells differentially correlate with T helper 1 and natural killer cells in peripheral blood. Hum Immunol 72:621–626

    Article  CAS  PubMed  Google Scholar 

  54. Clark DA, Banwatt D, Chaouat G (1993) Stress-triggered abortion in mice prevented by alloimmunization. Am J Reprod Immunol 29:141–147

    Article  CAS  PubMed  Google Scholar 

  55. Clark DA, Blois S, Kandil J, Handjiski B, Manuel J, Arck PC (2005) Reduced indoleamine 2,3-dioxygenase versus increased Th1/Th2 cytokine ratios as a basis for occult and clinical pregnancy failure in mice and humans. Am J Reprod Immunol 54:203–216

    Article  CAS  PubMed  Google Scholar 

  56. Clark DA, Yu G, Arck PC, Levy GA, Gorczynski RM (2003) MD-1 is a critical part of the mechanism causing Th1-cytokine-triggered murine fetal loss syndrome. Am J Reprod Immunol 49:297–307

    Article  PubMed  Google Scholar 

  57. Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 28:1191–1193

    Article  Google Scholar 

  58. Mellor AL, Sivakuman J, Chandler P, Smith K, Molina H, Mao D, Munn DH (2001) Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2:64–68

    Article  CAS  PubMed  Google Scholar 

  59. Sedlmayr P, Blaschitz A, Stocker R (2014) The role of placental tryptophan catabolism. Front Immunol 5:230. doi:10.3389/fimmu.2014.00239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Arck PC, Ferrick DA, Steele-Norwood D, Croitoru K, Clark DA (1997) Murine T cell determination of pregnancy outcome. I. Effects of strain, αβ T cell receptor, γδ T cell receptor and γδ T cell subsets. Am J Reprod Immunol 37:492–502

    Article  CAS  PubMed  Google Scholar 

  61. Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5:266–271

    Article  CAS  PubMed  Google Scholar 

  62. Heyborne K, Fu YX, Nelson A, Farr A, O’Brien R, Born W (1994) Recognition of trophoblasts by γδ T cells. J Immunol 153:2918–2976

    CAS  PubMed  Google Scholar 

  63. Guerin LR, Moldenhauer LM, Prins JR, Bromfield JJ, Hayball JD, Robertson SA (2011) Seminal fluid regulates accumulation of FOXP3+ regulatory T cells in the preimplantation mouse uterus through expanding the FOXP3+ cell pool and CCL19-mediated recruitment. Biol Reprod 85:397–408

    Article  CAS  PubMed  Google Scholar 

  64. Clark DA, Rahmati M, Bensussan A, Markert UR, Chaouat G (2013) Seminal plasma peptides may determine maternal immune response that alters success or failure of pregnancy in the abortion-prone CBAxDBA/2 model. J Reprod Immunol 99:46–53

    Article  CAS  PubMed  Google Scholar 

  65. Kahn DA, Baltimore D (2010) Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance. Proc Natl Acad Sci U S A 107:9299–9304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kallikourdis M, Betz AG (2007) Periodic accumulation of regulatory T cells in the uterus: preparation for implantation of the semi-allogeneic fetus? PLoS ONE 4:e382

    Article  CAS  Google Scholar 

  67. Kallikourdis M, Andersen KG, Welch KA, Betz AG (2007) Alloantigen-enhanced accumulation of CCR5+ ‘effector’ regulatory T cells in the gravid uterus. Proc Natl Acad Sci U S A 104:594–599

    Article  CAS  PubMed  Google Scholar 

  68. Chen T, Darrasse-Jeze G, Bergot A-S, Courau T, Churlaud G, Valdivia K, Strominger JL, Ruocco MG, Chaouat G, Klatzmann D (2013) Self-specific memory regulatory T cells protect embryos at implantation in mice. J Immunol 191:2273–2281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shima T, Sasaki T, Itoh M, Nakashima A, Ishii N, Sugamura K, Saito S (2010) Regulatory T cells are necessary form implantation and maintenance of early pregnancy but not late pregnancy in allogeneic mice. J Reprod Immunol 85:121–129

    Article  CAS  PubMed  Google Scholar 

  70. Beer AE, Billingham RE (1974) Host responses to intrauterine tissue, cellular and fetal allografts. J Reprod Fertil Suppl 21:59–88

    Google Scholar 

  71. Mincheva-Nilsson L, Hammarstrom S, Hammarstrom ML (1992) Human decidual leukocytes from early pregnancy shown high numbers of γδ+ cells and show selective down-regulation of alloreactivity. J Immunol 149:2203–2211

    CAS  PubMed  Google Scholar 

  72. Sasaki Y, Sasaki M, Miyazaki S, Higuma S, Shiozaki A, Saito S (2004) Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Molec Hum Reprod 10:347–353

    Article  CAS  PubMed  Google Scholar 

  73. Nakagawa K, Kwak-Kim J, Ota K, Kuroda K, Hisano M, Sugiyama R, Yamaguchi K (2015) Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood TH1/TH2 cell ratios. Am J Reprod Immunol 73:353–361

    Article  CAS  PubMed  Google Scholar 

  74. Wurfel W, Santjohanser C, Hirv K, Buhl M, Men O, Laubert I, von Hertwig I, Fiedler K, Krusmann J, Krusmann G (2010) High pregnancy rates with administration of granulocyte colony-stimulating factor in ART-patients with repetitive implantation failure and lacking killer-cell immunoglobulin-like receptors. Hum Reprod 25:2151–2152

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Scarpellini F, Sbracia F (2009) Use of colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomized controlled trial. Hum Reprod 11:2703–2708

    Article  CAS  Google Scholar 

  76. Chaouat G, Clark DA, Wegmann TG (1988) Genetic aspects of the CBA × DBA/2 and B10 × B10.A models of murine pregnancy failure and its prevention by lymphocyte immunisation. In: Beard RW, Sharp F (eds) Early pregnancy loss: mechanisms and treatment. Peacock Press, Ashton-Under-Lyne, pp 89–102

    Chapter  Google Scholar 

  77. Clark DA, Coulam CB, Daya S, Chaouat G (2001) Unexplained sporadic and recurrent miscarriage in the new millennium: a critical analysis of immune mechanisms and treatments. Hum Reprod 7:501–511

    Article  CAS  Google Scholar 

  78. Zenclussen AC, Gerlof K, Zenclussen M, Sollwedel A, Bertoja AZ, Ritter T, Kotsch K, Leber J, Volk HD (2005) 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 166:811–822

    Article  PubMed  PubMed Central  Google Scholar 

  79. Idali F, Rezaeenia S, Fatemi R, Naderi MM, Farzi M, Zarnani AH, Jeddi Tehrani M (2015) In vitro generated CD4+CD25+ regulatory T cells prevented fetal rejection in abortion-prone mice. J Reprod Immunol 111:10

    Article  Google Scholar 

  80. Clark DA, Fernandez J, Banwatt D (2008) Prevention of spontaneous abortion in the CBAxDBA/2 mouse model by intravaginal TGF-β and local recruitment of CD4+8+FOXP3+ cells. Am J Reprod Immunol 59:525–534 ((2008) erratum. Am J Reprod Immunol 60:90)

    Article  PubMed  Google Scholar 

  81. Clark DA, Chaouat G, Mogil R, Wegmann TG (1994) Prevention of spontaneous abortion in DBA/2-mated CBA/J mice by GM-CSF involves CD8+ T cell-dependent suppression of natural effector cells. Cell Immunol 154:143–152

    Article  CAS  PubMed  Google Scholar 

  82. Chaouat G, Petitbarat M, Bulla R, Dubanchet S, Valdivia K, Ledee N, Steffen T, Jensenius JC, Tedesco F (2009) Early regulators in abortion and implications for a preeclampsia model. J Reprod Immunol 82:132–141

    Article  CAS  Google Scholar 

  83. Kennedy TG, Gillio-Meina C, Pang SH (2007) Prostaglandins and the initiation of blastocyst implantation and decidualization. Reproduction 134:635–643

    Article  CAS  PubMed  Google Scholar 

  84. Clark DA, Foerster K, Fung L, He W, Lee L, Mendicino M, Markert UR, Gorczynski RM, Marsden PA, Levy GA (2004) The Fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction. Molec Hum Reprod 10:99–108

    Article  CAS  PubMed  Google Scholar 

  85. Endo Y, Nakazawa N, Iwaki D, Takahashi M, Matsushita M, Fujita T (2010) Interactions of ficolin and mannose-binding lectin with fibrinogen/fibrin augment the lectin complement pathway. J Innate Immun 2:33–42

    Article  CAS  PubMed  Google Scholar 

  86. Girardi G, Yarilin D, Thurman JM, Holers VM, Dalmon JE (2006) Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 203:2165–2175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Arck PC, Ferrick DA, Steele-Norwood D, Egan PJ, Croitoru K, Carding S, Dietl J, Clark DA (1999) Murine T cell determinants of pregnancy outcome. II. Distinct Th1 and Th2/3 populations of Vγ1+δ6+ T cells influence success or failure of pregnancy in CBA X DBA/2 matings. Cell Immunol 196:71–79

    Article  CAS  PubMed  Google Scholar 

  88. Clark DA, Lea RG, Podor T, Daya S, Banwatt D, Harley C (1991) Cytokines determine the success or failure of pregnancy. Ann N Y Acad Sci 626:524–536

    Article  CAS  PubMed  Google Scholar 

  89. Clark DA (1991) Controversies in reproductive immunology. Crit Rev Immunol 11:215–247

    CAS  PubMed  Google Scholar 

  90. Clark DA, Croitoru K (2001) Th1/Th2,3 imbalance due to cytokine-producing NK, γδT, and NK-γδT cells in murine pregnancy decidua in success or failure of pregnancy. Am J Reprod Immunol 45:257–265

    Article  CAS  PubMed  Google Scholar 

  91. Saito S, Shiozaki A, Sasaki Y, Nakashima A, Shima T, Ito M (2007) Regulatory T cells and regulatory natural killer (NK) cells play important roles in feto-maternal tolerance. Sem Immunopath 29:115–122

    Article  CAS  Google Scholar 

  92. Karimi K, Salano ME, Ashkar AA, Ho H, Steidle E-M, McVey Neufeld K-A, Hecher K, Bienenstock J, Arck PC (2012) Regulation of pregnancy maintenance and fetal survival in mice by CD27low mature NK cells. J Mol Med 90:1047–1057

    Article  CAS  PubMed  Google Scholar 

  93. Regaterio FS, Howie D, Cobbold SP, Waldmann H (2011) TGF-beta in transplantation tolerance. Curr Opin Immunol 23:660–669

    Article  CAS  Google Scholar 

  94. Chaouat G, Meliani AA, Martal J, Raghupathy R, Elliot J, Mosmann T, Wegmann TG (1995) IL-10 prevents naturally occurring fetal loss in the CBA × DBA/2 mating combination, and local defect in IL-10 production in the abortion-prone combination is corrected by in vivo injection of IFN-τ. J Immunol 154:4261–4268

    CAS  PubMed  Google Scholar 

  95. Friebe A, Douglas AJ, Solano E, Blois SM, Hagen E, Pliet R, Klapp BF, Clark DA, Arck PC (2011) Neutralization of LPS or blockage of TLR4 signaling prevents stress-triggered abortions in murine pregnancy. J Molec Med 89:689–699

    Article  CAS  PubMed  Google Scholar 

  96. Murphy SP, Fast LD, Hanna NN, Sharma S (2005) Uterine NK cells mediate inflammation-induced fetal demise in IL-10-null mice. J Immunol 175:4084–4090

    Article  CAS  PubMed  Google Scholar 

  97. Clark DA, Chaouat G, Wong K, Gorczynski RM, Kinsky R (2010) Tolerance mechanisms in pregnancy: a reappraisal of the role of Class I paternal MHC antigens. Am J Reprod Immunol 63:93–103

    Article  CAS  PubMed  Google Scholar 

  98. Thaxton JE, Nevers T, Lippe EO, Blois SM, Saito S, Sharma S (2013) NKG2D blockade inhibits poly (I:C)-triggered fetal loss in wild type but not in IL-10−/− mice. J Immunol 190:3639–3647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Clark DA, Chaouat G, Gorczynski RM (2002) Thinking outside the box: mechanisms of environmental selective pressures on the outcome of the materno-fetal relationship. Am J Reprod Immunol 47:275–282

    Article  PubMed  Google Scholar 

  100. Clark DA, Manuel J, Lee L, Chaouat G, Gorczynski RM, Levy GA (2004) Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA × DBA/2 mouse model. I. Synergistic effect of LPS and (TNF-α + IFN-γ) on pregnancy loss. Am J Reprod Immunol 52:370–387

    Article  PubMed  Google Scholar 

  101. Clark DA (2008) Immunological factors in pregnancy wastage: fact or fiction. Am J Reprod Immunol 59:277–300

    Article  CAS  PubMed  Google Scholar 

  102. Clark DA, Chaouat G, Arck PC, Mittruecker HW, Levy GA (1998) The cutting edge: cytokine-dependent abortion in CBA X DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase. J Immunol 160:545–549

    CAS  PubMed  Google Scholar 

  103. Amara U, Rittirsch D, Flierl M, Bruckner U, Klos A, Gebhard F, Lambris JD, Huber-Lang M (2008) Interaction between the coagulation and complement system. Adv Exp Med Biol 632:71–79

    CAS  PubMed  PubMed Central  Google Scholar 

  104. DiStasi MR, Ley K (2009) Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. Trends Immunol 30:547–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Simmons EL, Russell PS (1966) The histocompatibility antigens of fertilized mouse eggs and trophoblast. Ann N Y Acad Sci 129:35–45

    Article  Google Scholar 

  106. Ferry BL, Sargent IL, Starkey PM, Redman CWG (1991) Cytotoxic activity against trophoblast and choriocarcinoma cells of large granular lymphocytes from human early pregnancy deciduas. Cell Immunol 132:140–149

    Article  CAS  PubMed  Google Scholar 

  107. Redecha P, Tilley R, Tencati M, Salmon JE, Kirchhofer D (2007) Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody-induced fetal injury. Blood 110:2423–2431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Clark DA, Ding J, Coulam CB, August C, Chaouat G, Levy GA (1999) The emerging role of immunoregulation of fibrinogen-related procoagulant fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans. Am J Reprod Immunol 42:37–43

    Article  CAS  PubMed  Google Scholar 

  109. Girardi G, Redecha P, Salmon JE (2004) Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat Med 10:1222–1226

    Article  CAS  PubMed  Google Scholar 

  110. Girardi G (2011) Role of tissue factor in pregnancy complications: crosstalk between coagulation and inflammation. Thrombosis Res 127(Suppl 3):S43–S46

    Article  CAS  Google Scholar 

  111. Yu G, Sun Y, Foerster K, Manuel J, Molina H, Levy GA, Gorczynski RM, Clark DA (2008) LPS-induced murine abortions require C5 but not C3, and are prevented by upregulating expression of the CD200 tolerance signaling molecule. Am J Reprod Immunol 60:135–140

    Article  PubMed  Google Scholar 

  112. Chaouat G, Menu E, Wegmann TG (1991) Role of lymphokines of the CSF family and of TNF, gamma interferon, and IL-2 in placental growth and fetal survival studied in 2 murine models of spontaneous abortion. In: Chaouat G, Mowbray J (eds) Biologie cellulaire et moléculaire de la relation materno fetale. Colloque INSERM 212 John Libbey Paris 1991 91–98

  113. Arck PC, Troutt AB, Clark DA (1997) Soluble receptors neutralizing TNF-α and IL1 block stress-triggered murine abortion. Am J Reprod Immunol 37:262–266

    Article  CAS  PubMed  Google Scholar 

  114. Safronova VG, Matveeva NK, Avkhacheva NV, Sidel’nikova VM, Van’ko LV, Sukhikh GT (2003) Changes in regulation of oxidase activity of peripheral blood granulocytes in women with habitual abortions. Bull Exp Biol Med 136:257–260

    Article  CAS  PubMed  Google Scholar 

  115. Fait V, Sela S, Ophir E, Kreutzer H, Shnaider O, Perri A, Khatib N, Dourleshter G, Tendler R, Bornstein J (2005) Peripheral polymorphonuclear leukocyte priming contributes to oxidative stress in early pregnancy. J Soc Gynecol Invest 12:46–49

    Article  CAS  Google Scholar 

  116. Kshirsagar SK, Alarn SM, Jasti S, Hodes H, Nauser T, Gilliam M, Billstrand C, Hunt JS, Petroff MG (2012) Immunomodulatory molecules are released from the first trimester and term placenta via exosomes. Placenta 33:982–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Svensson J, Jenmalm MC, Matussek A, Geffers R, Berg G, Ernerudh J (2011) Macrophages at the fetal-maternal interface express markers of alternative activation and induced by M-CSF and IL-10. J Immunol 187:3671–3682

    Article  CAS  PubMed  Google Scholar 

  118. Nkashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S (2010) Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol 64:4–11

    Google Scholar 

  119. Winger EE, Reed J (2008) Treatment with tumor necrosis factor inhibitors and intravenous immunoglobulin improves birth rates in women with recurrent spontaneous abortion. Am J Reprod Immunol 60:8–16

    Article  CAS  PubMed  Google Scholar 

  120. Winger EE, Reed JL, Ashoush S, El-Touky T, Ahuja S, Taranissi M (2011) Degree of TNF-alpha/IL-10 cytokine elevation correlates with IVF success rates in women undergoing treatment with Adalimumab (Humira) and IVIG. Am J Reprod Immunol 65:610–618

    Article  CAS  PubMed  Google Scholar 

  121. Clark DA (2011) The power of observation. Am J Reprod Immunol 66:71–65 (erratum 66:162)

    Article  CAS  PubMed  Google Scholar 

  122. Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA (2012) TGF-β mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 189:1024–1035

    Article  CAS  PubMed  Google Scholar 

  123. Clark DA, Chaouat G (2012) Regulatory T cells and reproduction: how do they do it? J Reprod Immunol 96:1–7

    Article  CAS  PubMed  Google Scholar 

  124. Clark DA, Gorczynski RM (2013) Immunological tolerance/acceptance of the semi-allogeneic embryo: decidual transforming growth factors and tolerance signalling molecules. In: Chaouat G, Sandra O, Ledee N (eds) Immunology of pregnancy 2013. Bentham (e-book), London, pp 540–558

    Google Scholar 

  125. Clark DA, Arredondo JL, Dhesy-Thind B (2015) The CD200 tolerance-signaling molecule and its receptor, CD200R1, are expressed in human placental villus trophoblast and in peri-implant decidua by 5 weeks gestation. J Reprod Immunol 112:20–23. doi:10.1016/j.jri.2015.05.005

    Article  CAS  PubMed  Google Scholar 

  126. Vacca P, Cantoni C, Vitale M, Prato C, Canegallo F, Fenoglio D, Ragni D, Moretta L, Mingari MC (2010) Crosstalk between decudual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression. Proc Natl Acad Sci U S A 107:11918–11923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Clark DA, Chaouat G (2005) Loss of surface CD200 on stored allogeneic leukocytes may impair anti-abortive effect in vivo. Am J Reprod Immunol 53:13–20

    Article  CAS  PubMed  Google Scholar 

  128. Clark DA, Ding J-W, Yu G, Levy GA, Gorczynski RM (2001) Fgl2 prothrombinase expression in trophoblasts and decidua triggers abortion but may be countered by OX-2. Mol Hum Reprod 7:185–194

    Article  CAS  PubMed  Google Scholar 

  129. Tamamoto T, Takahashi Y, Kase N, Mori H (1999) Decidual natural killer cells in recurrent spontaneous abortion with normal chromosome content. Am J Reprod Immunol 41:337–342

    Article  Google Scholar 

  130. Inada K, Shima T, Nakashima A, Aoki K, Ito M, Saito S (2013) Characterization of regulatory T cells in decidua of miscarriage cases with abnormal or normal chromosomal content. J Reprod Immunol 97:104–111

    Article  CAS  PubMed  Google Scholar 

  131. Van den Heuvel MJ, Peralta CG, Hatta K, Han VK, Clark DA (2007) Decline in number of elevated blood CD3+ CD56+ NKT cells in response to IVIG treatment correlates with successful pregnancy. Am J Reprod Immunol 58:447–457 (Erratum 58:547)

    Article  PubMed  CAS  Google Scholar 

  132. Coulam CB, Acacio B (2012) Does immunotherapy for treatment of reproductive failure enhance live births? Am J Reprod Immunol 67:296–304

    Article  CAS  PubMed  Google Scholar 

  133. Kim DJ, Lee SK, Kim JY, Na BJ, Hur SE, Lee M, Kwak-Kim J (2014) Intravenous immunoglobulin G modulates peripheral blood Th17 and Foxp3+ regulatory T cells in women with recurrent pregnancy loss. Am J Reprod Immunol 71:441–450

    Article  CAS  PubMed  Google Scholar 

  134. Clark DA (2012) The end of evidence-based medicine? Implammopharmacology 20:187–193

    Article  Google Scholar 

  135. RMITG (The Recurrent Miscarriage Immunotherapy Trialists Group), Coulam C, Clark DA, Collins J, Scott JR, Schlesselman JS, Aoki K, Cauchi MN, Lim D, Christiansen OB, Grunnet N, Cowchock S, Smith JB, Daya S, Gatenby P, Camerson K, Gill TJ, Ho HN, Georgieva R, Belchev D, Kilpatrick DC, Liston W, Mowbray JF, Underwood J, Parazzini F, Crosignani PG, Rezenkoff MF, Koyama FS (1994) Worldwide collaborative observational study and meta-analysis on allogenic leukocyte immunotherapy for recurrent spontaneous abortion. Am J Reprod Immunol 32:55–72

    Article  Google Scholar 

  136. Clark DA (2011) Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: methodologic problems. Hum Reprod 26:2586–2587

    Article  CAS  PubMed  Google Scholar 

  137. Clark DA, Daya S, Coulam CB, Gunby J and The Recurrent Miscarriage Immunotherapy Trialists Group (1996) Implications of abnormal human trophoblast karyotype for the evidence-based approach to the understanding, investigation, and treatment of recurrent spontaneous abortion. Am J Reprod Immunol 35:495–498

    Article  Google Scholar 

  138. Clark DA (2009) An observational study on the role of cell surface CD200 in efficacy of paternal mononuclear leukocyte immunotherapy in recurrent pregnancy loss. Am J Reprod Immunol 61:75–84

    Article  PubMed  Google Scholar 

  139. Girardi G (2014) Can statins prevent pregnancy complications? J Reprod Immunol 101–102:161–167

    Article  PubMed  CAS  Google Scholar 

  140. Hot A, Lavocat F, Lenief V, Miossec P (2013) Simivistatin inhibits the pro-inflammatory and pro-thrombotic effects of IL-17 and TNF-alpha on endothelial cells. Ann Rheum Dis 72:754–760

    Article  CAS  PubMed  Google Scholar 

  141. Mier-Cabrera J, Jimenez-Zamudio L, Garcia-Latorre E, Cruz-Orozco E, Hernandez-Guerrero C (2011) Quantitative and qualitative peritoneal immune profiles, T cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis. BJOG 118:6–16

    Article  CAS  PubMed  Google Scholar 

  142. Hou Z, Sun L, Gao L, Liao L, Mao Y, Lui J (2009) Cytokine array analysis of peritoneal fluid between women with endometriosis of different stages and those without endometriosis. Biomarkers 14:604–618

    Article  CAS  PubMed  Google Scholar 

  143. Ulukus M, Cakmak H, Arici A (2006) The role of the endometrium in endometriosis. J Soc Gynecol Invest 13:467–476

    CAS  Google Scholar 

  144. Szyllo K, Tchorzewski H, Banasik M, Glowacka E, Kamer-Bartosinska A (2003) The involvement of T lymphocytes in the pathogenesis of endometriotic tissues overgrowth in women with endometriosis. Mediat Inflam 12:131–138

    Article  CAS  Google Scholar 

  145. Wu MY, Ho HN (2003) The role of cytokines in endometriosis. Am J Reprod Immunol 49:285–296

    Article  PubMed  Google Scholar 

  146. Kalu E, Sumar N, Giannopoulos T, Patel P, Croucher C, Sherriff E, Bansal A (2007) Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis. J Obstet Gynaecol Res 33:490–495

    Article  CAS  PubMed  Google Scholar 

  147. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A (2008) Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril 90:247–257

    Article  CAS  PubMed  Google Scholar 

  148. Gomez-torres MJ, Acien P, Campos A, Velasco I (2002) Embryotoxicity of periotoneal fluid in women with endometriosis. Its relation with cytokines and lymphocyte populations. Hum Reprod 17:777–781

    Article  PubMed  Google Scholar 

  149. Iwabe T, Harada T, Terakawa N (2002) Role of cytokines in endometriosis-associated infertility. Gynecol Obstet Invest 53(Suppl 1):19–25

    Article  CAS  PubMed  Google Scholar 

  150. Faber BM, Chegini N, Mahony MC, Coddington CC 3rd (2001) Macrophage secretory products and sperm zona pellucia binding. Obstet Gynecol 98:668–673

    CAS  PubMed  Google Scholar 

  151. Chen YI, Wu HH, Liau WT, Tsai CY, Tsai HW, Chao KC, Sung YI, Li HY (2013) A tumor necrosis-factor-alpha inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid. Fertil Steril 100:1476–1485

    Article  CAS  PubMed  Google Scholar 

  152. Randall GW, O’Connor EF, Grant PA (1991) Synergy between tumor necrosis factor and endotoxin decreases early embryo development in vitro. J In Vitro Fert Embryo Transf 8:304–307

    Article  CAS  PubMed  Google Scholar 

  153. Lalitkumar PG, Sengupta J, Ghosh D (2005) Effect of tumor necrosis factor-alpha (TNF-alpha) on protein synthesis by mouse preimplantation stage embryos in vitro. Indian J Physiol Pharmacol 49:139–147

    CAS  PubMed  Google Scholar 

  154. Glabowski W, Kuzawa R, Wiszniewska B, Baczkowshi T, Marxhlewicz M, Brelik P (2005) Growth factor effects on preimplantation development of mouse embryos exposed to tumor necrosis factor alpha. Reprod Biol 5:83–99

    PubMed  Google Scholar 

  155. Noriega J, Bedaiwy M, Sharma R, Falcone T (2004) Effect of tumor necrosis factor-alpha blocker (infliximab) on blastocyst development in vitro. Fertil Steril 81:1704–1706

    Article  PubMed  CAS  Google Scholar 

  156. Wuu YD, Pampfer S, Becquet P, Vanderheyden I, Lee KH, De Hertogh R (1999) Tumor necrosis factor alpha decreases viability of mouse blastocysts in vitro and in vivo. Biol Reprod 60:479–483

    Article  CAS  PubMed  Google Scholar 

  157. Sawartari Y, Horii T, Hoshiai H (1993) Oily contrast medium as a therapeutic agent for infertility because of mild endometriosis. Fertil Steril 59:907–911

    Article  Google Scholar 

  158. Court KA, Dare AJ, Hadden WE, Weston-Webb M, Sim RG, Johnson NP (2014) Establishment of lipiodol as a fertility treatment—prospective study of the complete innovative treatment data set. Aust N Zealand J Obstet Gynaecol 54:13–19

    Article  CAS  Google Scholar 

  159. Lin YJ, Lai MD, Lei HY, Wing LY (2006) Neutrophils and macrophages promote angiogenesis in the early stage of endometriosis in a mouse model. Endocrinology 147:1278–1286

    Article  CAS  PubMed  Google Scholar 

  160. Chen QH, Zhou WD, Su ZY, Huang QS, Jiang JN, Chen QX (2010) Change of proinflammatory cytokines follows certain patterns after induction of endometriosis in a mouse model. Fertil Steril 93:1448–1454 (erratum 94:1948)

    Article  CAS  PubMed  Google Scholar 

  161. Szymanowski K, Niepsuj-Binias J, Dera-Symanowska A, Wolun-Cholewa N, Yantczenko A, Florek E, Opala T, Murawski M, Wiktorowicz K (2013) An influence of immunomodulation on Th1 and Th2 immune response in endometriosis in an animal model. BioMed Res Int 2013:848492

    Article  Google Scholar 

  162. Kondo W, Dal Lago EA, Francisco JC, de Noronha L, Martins AP, de Azevedo ML, Ferreira CC, Maestrelli P, Olandoski M, Guarita-Souza LC, do Amaral VF (2011) Effect of bone marrow derived-mononuclear stem cell transplantation in the growth, VEGF-T and TNF-alpha expression of endometrial implants in Wistar rats. Eur J Obstet Gynecol Reprod Biol 158:298–304

    Article  CAS  PubMed  Google Scholar 

  163. Umezawa M, Sakata C, Tanaka N, Kudo S, Tabata M, Takeda K, Ihara T, Sugamata M (2008) Cytokine and chemokines expression in rat endometriosis is similar to than in human endometriosis. Cytokine 43:105–109

    Article  CAS  PubMed  Google Scholar 

  164. Islimye M, Kilic S, Zulfikaroglu E, Topcu O, Zergeroglu S, Batioglu S (2011) Regression of endometrial autografts in a rat model of endometriosis treated with etanercept. Eur J Obstet Gynecol Reprod Biol 159:184–189

    Article  CAS  PubMed  Google Scholar 

  165. Falconer H, Mwenda JM, Chai DC, Song XY, Cornille FJ, Bergqvist A, Fried G, D’Hooghe TM (2008) Effects of anti-TNF-mAb treatment on pregnancy in baboons with induced endometriosis. Fertil Steril 89(Suppl 1):1537–1545

    Article  CAS  PubMed  Google Scholar 

  166. Trogstad L, Magnus P, Stoltenberg C (2011) Pre-eclampsia: risk factors and causal models. Best Pract Res Clin Obstet Gynaecol 25:329–342

    Article  PubMed  Google Scholar 

  167. Redman CW, Sargent IL, Staff AC (2014) IFPA Senior Award Lecture: making sense of pre-eclampsia—two placental causes of preeclampsia. Placenta 28:S20–S25

    Article  Google Scholar 

  168. Wallace AE, Fraser R, Cartwright JE (2012) Extravillous trophoblast and decidual natural killer cells: a remodeling partnership. Hum Reprod Update 18:458–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Cotechini T, Komisarenko M, Sperou A, Macdonald-Goodfellow S, Adams MA, Graham CH (2014) Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J Exp Med 211:165–179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Ahmed A, Singh J, Kahn Y, Seshan SV, Girardi G (2010) A new mouse model to explore therapies for preeclampsia. PLoS One 5:e13663. doi:10.1371/journal.pone.0012663

  171. Kumasawa K, Ikawa M, Kidoya H, Hasuwa H, Saito-Fujita T, Morioka Y, Takukara N, Kimura T, Okabe M (2011) Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. Proc Natl Acad Sci U S A 108:1451–1455

    Article  CAS  PubMed  Google Scholar 

  172. Lefkou E, Mamopoulos A, Fragakis N, Dagkis T, Vosnakis C, Nounopoulos E, Rousso D, Girardi G (2014) Clinical improvement and successful pregnancy in a preeclamptic patient with antiphospholipid syndrome treated with pravastatin. Hypertension 63:e118–e119

    Article  CAS  PubMed  Google Scholar 

  173. Kelishadi R, Haghdoost AA, Jamshidi F, Aliramezany M, Moosazadeh M (2015) Low birth weight or rapid catch-up growth: which is more associated with cardiovascular disease and its risk factors in later life? A systematic review and cryptanalysis. Paediatr Int Child Health 35:110–125

    Article  PubMed  Google Scholar 

  174. Wegmann TG (1988) Maternal T cells promote placental growth and prevent spontaneous abortion. Immunol Lett 17:297–302

    Article  CAS  PubMed  Google Scholar 

  175. Mowbray JF, Underwood JL (1991) In: Chaouat G, Mowbray JF (eds) Effect of paternal lymphocyte immunization on birthweight and pregnancy outcome. In: Chaouat, G., Mowbray JF (eds) Cellular and molecular biology of the materno-fetal relationship. INSERM Colloques vol 212, John Libby Eurotext, 295–302

  176. Bromfield JJ, Schjenken JE, Chin PY, Care AS, Jasper MJ, Robertson SA (2014) Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype of offspring. Proc Natl Acad Sci U S A 111:2200–2205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Clark DA (1994) Does immunological intercourse prevent pre-eclampsia? Lancet 344:969–970

    Article  CAS  PubMed  Google Scholar 

  178. Colucci F, Kieckbusch J (2015) Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus. Trends Molec Med 21:60–67

    Article  CAS  Google Scholar 

  179. Madeja Z, Yadi H, Apps R, Doulenouar S, Roper S, Gardner L, Moffett A, Colucci F, Hemberger M (2011) Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci U S A 108:4012–4017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Tornblom SA, Klimaviciute A, Bystrom B, Chromek M, Brauner A, Ekman-Ordeberg G (2005) Non-infected preterm parturition is related to increased concentrations of IL-6, Il-8, and MCP-1 in human cervix. Reprod Biol Endocrinol 3:39

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  181. Gravett MG, Hitti J, Hess DL, Eschenbach DA (2000) Intrauterine infection and preterm delivery: evidence for activation of the fetal hypothalamic-pituitary-adrenal axis. Am J Obstet Gynecol 182:1404–1413

    Article  CAS  PubMed  Google Scholar 

  182. Murphy SP, Hanna NH, Fast LD, Shaw SK, Berg G, Padbury JF, Romero R, Sharma S (2009) Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery. Am J Obstst Gynecol 200:308.e1–3408.e9

    Article  Google Scholar 

  183. Phillippe M, Diamond AK, Sweet LM, Oppenheimer KH, Bradley DF (2011) Expression of coagulation-related protein genes during LPS-induced preterm delivery in the pregnant mouse. Reprod Sci 18:1071–1079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Boyle AK, Rinaldi SF, Thomson AJ, Rossi AG, Saunders PT, Norman JE (2015) Statin treatment in a novel infection-induced mouse model of preterm birth. J Reprod Immunol 111:16

    Article  Google Scholar 

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  1. Department of Medicine, Health Sciences Center Rm 3H1E, McMaster University, 1280 Main St. West, Hamilton, ON, L8S 4K1, Canada

    David A. Clark

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This article is related to Fetomaternal Cross Talk and its Effect on Pregnancy Maintenance Maternal and Offspring Health – Guest Editor: Petra Arck

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Clark, D.A. Mouse is the new woman? Translational research in reproductive immunology. Semin Immunopathol 38, 651–668 (2016). https://doi.org/10.1007/s00281-015-0553-x

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